Chapter 27

Chapter 27 - Chapter 27 Amino Acids Peptides Amino and...

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Unformatted text preview: Chapter 27 Amino Acids, Peptides, Amino and Proteins and Dr. Wolf's CHM 424 27- 1 27.1 Classification of Amino Acids Dr. Wolf's CHM 424 27- 2 Fundamentals While their name implies that amino acids are While compounds that contain an —NH2 group and a compounds —CO2H group, these groups are actually —CO group, present as —NH3+ and —CO2– respectively. present They are classified as α, β, γ , etc. amino acids They etc amino according the carbon that bears the nitrogen. according Dr. Wolf's CHM 424 27- 3 Amino Acids + NH3 α CO2– + – H3NCH2CH2CO2 β + – H3NCH2CH2CH2CO2 γ Dr. Wolf's CHM 424 an α-amino acid that is an an intermediate in the biosynthesis of ethylene a β-amino acid that is one of the structural units present in coenzyme A a γ -amino acid involved in the transmission of nerve impulses 27- 4 The 20 Key Amino Acids More than 700 amino acids occur naturally, but More 20 of them are especially important. 20 These 20 amino acids are the building blocks of These proteins. All are α-amino acids. They differ in respect to the group attached to They the α carbon. These 20 are listed in Table 27.1. Dr. Wolf's CHM 424 27- 5 Table 27.1 + H3N H C O C – O R R The amino acids obtained by hydrolysis of The proteins differ in respect to R (the side chain). (the The properties of the amino acid vary as the The structure of R varies. Dr. Wolf's CHM 424 27- 6 Table 27.1 + H3N H C O C – O R R The major differences among the side chains The concern: concern: Size and shape Electronic characteristics Dr. Wolf's CHM 424 27- 7 Table 27.1 General categories of α-amino acids General nonpolar side chains polar but nonionized side chains acidic side chains basic side chains Dr. Wolf's CHM 424 27- 8 Table 27.1 General categories of α-amino acids General nonpolar side chains polar but nonionized side chains acidic side chains basic side chains Dr. Wolf's CHM 424 27- 9 Table 27.1 Glycine (Gly or G) + H3N H C O C – O H Glycine is the simplest amino acid. It is the only Glycine one in the table that is achiral. one In all of the other amino acids in the table the α In carbon is a chirality center. carbon Dr. Wolf's CHM 424 27- 10 Table 27.1 + H3N H C O C – O CH3 Alanine (Ala or A) Alanine, valine, leucine, and isoleucine have Alanine, alkyl groups as side chains, which are nonpolar and hydrophobic. and Dr. Wolf's CHM 424 27- 11 Table 27.1 + H3N H C O C – O CH(CH3)2 Valine (Val or V) Dr. Wolf's CHM 424 27- 12 Table 27.1 + H3N H C O C – O CH2CH(CH3)2 Leucine (Leu or L) Dr. Wolf's CHM 424 27- 13 Table 27.1 + H3N H C O C – O CH3CHCH2CH3 Isoleucine (Ile or I) Dr. Wolf's CHM 424 27- 14 Table 27.1 + H3N H C O C – O CH3SCH2CH2 Methionine (Met or M) The side chain in methionine is nonpolar, but The the presence of sulfur makes it somewhat polarizable. polarizable. Dr. Wolf's CHM 424 27- 15 Table 27.1 + H2N H2C H C C H2 O C CH2 – O Proline (Pro or P) Proline is the only amino acid that contains a Proline secondary amine function. Its side chain is nonpolar and cyclic. nonpolar Dr. Wolf's CHM 424 27- 16 Table 27.1 + H3N H C CH2 O C – O Phenylalanine (Phe or F) (Phe The side chain in phenylalanine (a nonpolar The amino acid) is a benzyl group. amino Dr. Wolf's CHM 424 27- 17 Table 27.1 Tryptophan + H3N H C CH2 (Trp or W) N H Dr. Wolf's CHM 424 O C – O The side chain in The tryptophan (a nonpolar amino acid) is larger and more polarizable than the benzyl group of phenylalanine. of 27- 18 Table 27.1 General categories of α-amino acids General nonpolar side chains polar but nonionized side chains acidic side chains basic side chains Dr. Wolf's CHM 424 27- 19 Table 27.1 + H3N H C O C – O CH2OH Serine (Ser or S) The —CH2OH side chain in serine can be OH involved in hydrogen bonding. involved Dr. Wolf's CHM 424 27- 20 Table 27.1 + H3N H C O C – O CH3CHOH Threonine (Thr or T) The side chain in threonine can be involved in The hydrogen bonding, but is somewhat more crowded than in serine. crowded Dr. Wolf's CHM 424 27- 21 Table 27.1 + H3N H C O C – O CH2SH Cysteine (Cys or C) The side chains of two remote cysteines can be The joined by forming a covalent S—S bond. joined Dr. Wolf's CHM 424 27- 22 Table 27.1 Tyrosine (Tyr or Y) + H3N H C CH2 O C – O The side chain of The tyrosine is similar to that of phenylalanine but can participate in hydrogen bonding. hydrogen OH OH Dr. Wolf's CHM 424 27- 23 Table 27.1 + H3N H C H2NCCH2 O O C – O Asparagine (Asn or N) The side chains of asparagine and glutamine The (next slide) terminate in amide functions that are polar and can engage in hydrogen bonding. polar Dr. Wolf's CHM 424 27- 24 Table 27.1 + H3N H C H2NCCH2CH2 O C – O Glutamine (Gln or Q) O Dr. Wolf's CHM 424 27- 25 Table 27.1 General categories of α-amino acids General nonpolar side chains polar but nonionized side chains acidic side chains basic side chains Dr. Wolf's CHM 424 27- 26 Table 27.1 + H3N H C – OCCH2 O O C – O Aspartic Acid (Asp or D) Aspartic acid and glutamic acid (next slide) exist Aspartic as their conjugate bases at biological pH. They are negatively charged and can form ionic bonds with positively charged species. bonds Dr. Wolf's CHM 424 27- 27 Table 27.1 + H3N – C OCCH2CH2 O Dr. Wolf's CHM 424 H O C – O Glutamic Acid (Glu or E) 27- 28 Table 27.1 General categories of α-amino acids General nonpolar side chains polar but nonionized side chains acidic side chains basic side chains Dr. Wolf's CHM 424 27- 29 Table 27.1 Lysine (Lys or K) + H3N H C O C – O + CH2CH2CH2CH2NH3 Lysine and arginine (next slide) exist as their Lysine conjugate acids at biological pH. They are positively charged and can form ionic bonds with negatively charged species. with Dr. Wolf's CHM 424 27- 30 Table 27.1 Arginine (Arg or R) + H3N H C O C – O CH2CH2CH2NHCNH2 + NH2 Dr. Wolf's CHM 424 27- 31 Table 27.1 Histidine (His or H) + H3N C CH2 N Dr. Wolf's CHM 424 H NH NH O C – O Histidine is a basic Histidine amino acid, but less basic than lysine and arginine. Histidine can interact with metal ions and can help move protons from one site to another. to 27- 32 27.2 Stereochemistry of Amino Stereochemistry Acids Acids Dr. Wolf's CHM 424 27- 33 Configuration of α-Amino Acids Configuration Glycine is achiral. All of the other amino acids Glycine in proteins have the L-configuration at their -configuration α carbon. carbon. – CO2 + H3N H R Dr. Wolf's CHM 424 27- 34 27.3 Acid-Base Behavior of Amino Acid-Base Acids Acids Dr. Wolf's CHM 424 27- 35 Recall While their name implies that amino acids are While compounds that contain an —NH2 group and a compounds —CO2H group, these groups are actually —CO group, present as —NH3+ and —CO2– respectively. present How do we know this? Dr. Wolf's CHM 424 27- 36 Properties of Glycine The properties of glycine: high melting point: (when heated to 233°C it decomposes before it melts) it solubility: soluble in water; not soluble in nonpolar solvent nonpolar more consistent with this than this •O • •• + H3NCH2C Dr. Wolf's CHM 424 •O • •• •• •– O• •• •• H2NCH2C •• OH •• 27- 37 Properties of Glycine The properties of glycine: high melting point: (when heated to 233°C it decomposes before it melts) it solubility: soluble in water; not soluble in nonpolar solvent nonpolar more consistent with this •O • •• + H3NCH2C Dr. Wolf's CHM 424 •• •– O• •• called a zwitterion or called zwitterion dipolar ion dipolar 27- 38 Acid-Base Properties of Glycine The zwitterionic structure of glycine also follows The from considering its acid-base properties. from A good way to think about this is to start with the good structure of glycine in strongly acidic solution, say pH = 1. say At pH = 1, glycine exists in its protonated form At (a monocation). (a •O • •• + H3NCH2C Dr. Wolf's CHM 424 •• OH •• 27- 39 Acid-Base Properties of Glycine Now ask yourself "As the pH is raised, which is Now the first proton to be removed? Is it the proton attached to the positively charged nitrogen, or is it the proton of the carboxyl group?" it You can choose between them by estimating You their respective pKas. their typical typical ammonium ion: pKa ~9 ion: Dr. Wolf's CHM 424 •O • •• + H3NCH2C •• OH •• typical typical carboxylic acid: pKa ~5 acid: 27- 40 Acid-Base Properties of Glycine The more acidic proton belongs to the CO2H group. It is the first one removed as the pH is raised. raised. •O • •• + H3NCH2C Dr. Wolf's CHM 424 •• OH •• typical typical carboxylic acid: pKa ~5 acid: 27- 41 Acid-Base Properties of Glycine Therefore, the more stable neutral form of Therefore, glycine is the zwitterion. glycine •O • •• + H3NCH2C •• •– O• •• •O • •• + H3NCH2C Dr. Wolf's CHM 424 •• OH •• typical typical carboxylic acid: pKa ~5 acid: 27- 42 Acid-Base Properties of Glycine The measured pKa of glycine is 2.34. Glycine is stronger than a typical carboxylic acid Glycine because the positively charged N acts as an electron-withdrawing, acid-strengthening substituent on the α carbon. •O • •• + H3NCH2C Dr. Wolf's CHM 424 •• OH •• typical typical carboxylic acid: pKa ~5 acid: 27- 43 Acid-Base Properties of Glycine A proton attached to N in the zwitterionic form of proton nitrogen can be removed as the pH is increased further. •O • •• + H3NCH2C •• •– O• •• HO – •O • •• •• H2NCH2C •• •– O• •• The pKa for removal of this proton is 9.60. This value is about the same as that for NH4+ (9.3). (9.3). Dr. Wolf's CHM 424 27- 44 Isoelectric Point pI •O • •• + H3NCH2C pKa = 2.34 •• OH •• •O • •• + H3NCH2C •• •– O• •• pKa = 9.60 •O • •• •• H2NCH2C Dr. Wolf's CHM 424 •• •– O• •• The pH at which the The concentration of the zwitterion is a maximum is called the isoelectric point. Its isoelectric Its numerical value is the average of the two pKas. The pI of glycine is 5.97. 5.97. 27- 45 Acid-Base Properties of Amino Acids One way in which amino acids differ is in One respect to their acid-base properties. This is the basis for certain experimental methods for separating and identifying them. separating Just as important, the difference in acid-base Just properties among various side chains affects the properties of the proteins that contain them. properties Table 27.2 gives pKa and pI values for amino acids with neutral side chains. acids Dr. Wolf's CHM 424 27- 46 Table 27.2 Amino Acids with Neutral Side Chains Amino Glycine + H3N H C H Dr. Wolf's CHM 424 O C – O pKa1 pKa2 pI = = = 2.34 2.34 9.60 5.97 27- 47 Table 27.2 Amino Acids with Neutral Side Chains Amino Alanine + H3N H C CH3 Dr. Wolf's CHM 424 O C – O pKa1 pKa2 pI = = = 2.34 2.34 9.69 6.00 27- 48 Table 27.2 Amino Acids with Neutral Side Chains Amino Valine + H3N H C O C – O CH(CH3)2 Dr. Wolf's CHM 424 pKa1 pKa2 pI = = = 2.32 2.32 9.62 5.96 27- 49 Table 27.2 Amino Acids with Neutral Side Chains Amino Leucine + H3N H C O C – O CH2CH(CH3)2 Dr. Wolf's CHM 424 pKa1 pKa2 pI = = = 2.36 2.36 9.60 5.98 27- 50 Table 27.2 Amino Acids with Neutral Side Chains Amino Isoleucine + H3N H C O C – O CH3CHCH2CH3 Dr. Wolf's CHM 424 pKa1 pKa2 pI = = = 2.36 2.36 9.60 5.98 27- 51 Table 27.2 Amino Acids with Neutral Side Chains Amino + H3N Methionine H C CH3SCH2CH2 Dr. Wolf's CHM 424 O C – O pKa1 pKa2 pI = = = 2.28 2.28 9.21 5.74 27- 52 Table 27.2 Amino Acids with Neutral Side Chains Amino Proline + H2N H2C Dr. Wolf's CHM 424 H C C H2 O C CH2 – O pKa1 pKa2 pI = = = 1.99 1.99 10.60 6.30 27- 53 Table 27.2 Amino Acids with Neutral Side Chains Amino Phenylalanine + H3N H C CH2 Dr. Wolf's CHM 424 O C – O pKa1 pKa2 pI = = = 1.83 1.83 9.13 5.48 27- 54 Table 27.2 Amino Acids with Neutral Side Chains Amino Tryptophan + H3N H C CH2 O C – O pKa1 pKa2 pI = = = 2.83 2.83 9.39 5.89 N Dr. Wolf's CHM 424 H 27- 55 Table 27.2 Amino Acids with Neutral Side Chains Amino Asparagine + H3N H C H2NCCH2 O C – O pKa1 pKa2 pI = = = 2.02 2.02 8.80 5.41 O Dr. Wolf's CHM 424 27- 56 Table 27.2 Amino Acids with Neutral Side Chains Amino + H3N Glutamine H C H2NCCH2CH2 O C – O pKa1 pKa2 pI = = = 2.17 2.17 9.13 5.65 O Dr. Wolf's CHM 424 27- 57 Table 27.2 Amino Acids with Neutral Side Chains Amino Serine + H3N H C O C CH2OH Dr. Wolf's CHM 424 – O pKa1 pKa2 pI = = = 2.21 2.21 9.15 5.68 27- 58 Table 27.2 Amino Acids with Neutral Side Chains Amino Threonine + H3N H C O C CH3CHOH Dr. Wolf's CHM 424 – O pKa1 pKa2 pI = = = 2.09 2.09 9.10 5.60 27- 59 Table 27.2 Amino Acids with Neutral Side Chains Amino Tyrosine Dr. Wolf's CHM 424 + H3N H C CH2 OH OH O C – O pKa1 pKa2 pI = = = 2.20 2.20 9.11 5.66 27- 60 Table 27.3 Amino Acids with Neutral Side Chains Amino Cysteine + H3N H C O C CH2SH Dr. Wolf's CHM 424 – O pKa1 pKa2 pI = = = 1.96 1.96 8.18 5.07 27- 61 Table 27.3 Amino Acids with Ionizable Side Chains Amino Aspartic acid + H3N H C – OCCH2 O C – O pKa1 pKa2 pKa3 pI = = = = 1.88 1.88 3.65 9.60 9.60 2.77 O For amino acids with acidic side chains, pI is the For average of pKa1 and pKa2. average Dr. Wolf's CHM 424 27- 62 Table 27.3 Amino Acids with Ionizable Side Chains Amino Glutamic acid + H3N H C – OCCH2CH2 O C – O pKa1 pKa2 pKa3 pI = = = = 2.19 2.19 4.25 9.67 9.67 3.22 O Dr. Wolf's CHM 424 27- 63 Table 27.3 Amino Acids with Ionizable Side Chains Amino + H3N H C O C – O + CH2CH2CH2CH2NH3 pKa1 pKa2 pKa3 pI = = = = 2.18 2.18 8.95 10.53 9.74 Lysine For amino acids with basic side chains, pI is the For average of pKa2 and pKa3. average Dr. Wolf's CHM 424 27- 64 Table 27.3 Amino Acids with Ionizable Side Chains Amino + H3N H C O C – O CH2CH2CH2NHCNH2 + NH2 pKa1 pKa2 pKa3 pI = = = = 2.17 2.17 9.04 12.48 10.76 Arginine Dr. Wolf's CHM 424 27- 65 Table 27.3 Amino Acids with Ionizable Side Chains Amino Histidine + H3N H C CH2 N Dr. Wolf's CHM 424 O C – O pKa1 pKa2 pKa3 pI = = = = 1.82 1.82 6.00 9.17 9.17 7.59 NH NH 27- 66 27.4 Synthesis of Amino Acids Dr. Wolf's CHM 424 27- 67 From α-Halo Carboxylic Acids From O CH3CHCOH + 2NH3 Br H2O O – CH3CHCO + NH4Br + NH3 (65-70%) Dr. Wolf's CHM 424 27- 68 Strecker Synthesis O CH3CH NH4Cl NaCN CH3CHC N NH2 1. H2O, HCl, heat 2. HO– O – CH3CHCO Dr. Wolf's CHM 424 + NH3 (52-60%) 27- 69 Using Diethyl Acetamidomalonate O O C C C CH3CH2O CH3CNH H OCH2CH3 O Can be used in the same manner as diethyl Can malonate (Section 21.7). malonate Dr. Wolf's CHM 424 27- 70 Example OO CH3CH2OCCCOCH2CH3 H CH3CNH O 1. NaOCH2CH3 2. C6H5CH2Cl 2. OO CH3CH2OCCCOCH2CH3 CH3CNH Dr. Wolf's CHM 424 O CH2C6H5 (90%) 27- 71 OO Example HOCCCOH –CO2 CH2C6H5 H3N + O HBr, H2O, heat HCCOH H3N + CH2C6H5 (65%) OO CH3CH2OCCCOCH2CH3 CH3CNH Dr. Wolf's CHM 424 O CH2C6H5 27- 72 27.5 Reactions of Amino Acids Dr. Wolf's CHM 424 27- 73 Acylation of Amino Group The amino nitrogen of an amino acid can be The converted to an amide with the customary acylating agents. acylating O + –+ H3NCH2CO O OO CH3COCCH3 O CH3CNHCH2COH Dr. Wolf's CHM 424 (89-92%) 27- 74 Esterification of Carboxyl Group The carboxyl group of an amino acid can be The converted to an ester. The following illustrates Fischer esterification of alanine. O + –+ H3NCHCO CH3CH2OH CH3 HCl O – Cl Dr. Wolf's CHM 424 + H3NCHCOCH2CH3 CH3 (90-95%) 27- 75 Ninhydrin Test Amino acids are detected by the formation of a purple Amino color on treatment with ninhydrin. ninhydrin O O OH OH OH O O + + H3NCHCO– R O RCH + CO2 + H2O + Dr. Wolf's CHM 424 O– N O O 27- 76 27.6 Some Biochemical Reactions of Amino Acids Dr. Wolf's CHM 424 27- 77 Biosynthesis of L-Glutamic Acid Biosynthesis O HO2CCH2CH2CCO2H + NH3 enzymes and reducing coenzymes HO2CCH2CH2CHCO2 – + NH3 This reaction is the biochemical analog of reductive This amination (Section 22.10). amination Dr. Wolf's CHM 424 27- 78 Transamination via L-Glutamic Acid Transamination via O HO2CCH2CH2CHCO2 – + CH3CCO2H + NH3 L-Glutamic acid acts as a source of the amine -Glutamic group in the biochemical conversion of α-keto acids to other amino acids. In the example to be shown, pyruvic acid is converted to L-alanine. shown, Dr. Wolf's CHM 424 27- 79 Transamination via L-Glutamic Acid Transamination via O HO2CCH2CH2CHCO2 – + CH3CCO2H + NH3 enzymes O HO2CCH2CH2CCO2H + CH3CHCO2 – + NH3 Dr. Wolf's CHM 424 27- 80 Mechanism O HO2CCH2CH2CHCO2 – + CH3CCO2H + NH3 The first step is imine formation between the amino group of L-glutamic acid and pyruvic amino acid. Dr. Wolf's CHM 424 27- 81 Mechanism O HO2CCH2CH2CHCO2 – + CH3CCO2H + NH3 – HO2CCH2CH2CHCO2 N Dr. Wolf's CHM 424 CH3CCO2– 27- 82 Formation of the imine is followed by proton Formation proton removal at one carbon and protonation of protonation another carbon. another H – HO2CCH2CH2CCO2 N Dr. Wolf's CHM 424 CH3CCO2– 27- 83 – HO2CCH2CH2CCO2 N CH3CCO2– H H – HO2CCH2CH2CCO2 N Dr. Wolf's CHM 424 CH3CCO2– 27- 84 – HO2CCH2CH2CCO2 N CH3CCO2– H Hydrolysis of the imine function gives α-keto glutarate and L-alanine. -keto Dr. Wolf's CHM 424 27- 85 – HO2CCH2CH2CCO2 N CH3CCO2– H H2O +NH3 – HO2CCH2CH2CCO2 O Dr. Wolf's CHM 424 + – CH3CCO2 H 27- 86 Biosynthesis of L-Tyrosine Biosynthesis L-Tyrosine is biosynthesized from L-phenylalanine. Tyrosine A key step is epoxidation of the aromatic ring to key give an arene oxide intermediate. arene CH2CHCO2 CH – + NH3 Dr. Wolf's CHM 424 27- 87 Biosynthesis of L-Tyrosine Biosynthesis CH2CHCO2 O – + NH3 O2, enzyme CH2CHCO2 CH – + NH3 Dr. Wolf's CHM 424 27- 88 Biosynthesis of L-Tyrosine Biosynthesis CH2CHCO2 O – + NH3 enzyme HO CH2CHCO2 – + NH3 Dr. Wolf's CHM 424 27- 89 Biosynthesis of L-Tyrosine Biosynthesis Conversion to L-tyrosine is one of the major Conversion -tyrosine metabolic pathways of L-phenylalanine. Individuals who lack the enzymes necessary to Individuals convert L-phenylalanine to L-tyrosine can suffer -phenylalanine -tyrosine from PKU disease. In PKU disease, Lphenylalanine is diverted to a pathway leading phenylalanine to phenylpyruvic acid, which is toxic. to Newborns are routinely tested for PKU disease. Newborns Treatment consists of reducing their dietary intake of phenylalanine-rich proteins. intake Dr. Wolf's CHM 424 27- 90 Decarboxylation Decarboxylation is a common reaction of αDecarboxylation amino acids. An example is the conversion of amino L-histidine to histamine. Antihistamines act by -histidine blocking the action of histamine. blocking N CH2CHCO2 CH N H Dr. Wolf's CHM 424 – + NH3 27- 91 Decarboxylation N CH2CH2 NH2 CH N H –CO2, enzymes N CH2CHCO2 CH N H Dr. Wolf's CHM 424 – + NH3 27- 92 Neurotransmitters The chemistry of the The brain and central nervous system is affected by neurotransmitters. neurotransmitters. Several important Several neurotransmitters are biosynthesized from L-tyrosine. + H3N H – CO2 H H OH L-Tyrosine Dr. Wolf's CHM 424 27- 93 Neurotransmitters The common name The of this compound is L-DOPA. It occurs -DOPA. naturally in the brain. It is widely prescribed to reduce the symptoms of Parkinsonism. Parkinsonism. + H3N H – CO2 H H HO OH L-3,4-Dihydroxyphenylalanine Dr. Wolf's CHM 424 27- 94 Neurotransmitters Neurotransmitters Dopamine is formed Dopamine by decarboxylation of L-DOPA. H H2N H H H HO OH Dopamine Dr. Wolf's CHM 424 27- 95 Neurotransmitters Neurotransmitters H H2N H H OH HO OH Norepinephrine Dr. Wolf's CHM 424 27- 96 Neurotransmitters Neurotransmitters H CH3NH H H OH HO OH Epinephrine Dr. Wolf's CHM 424 27- 97 27.7 Peptides Dr. Wolf's CHM 424 27- 98 Peptides Peptides are compounds in which an amide Peptides bond links the amino group of one α-amino acid -amino and the carboxyl group of another. and An amide bond of this type is often referred to An as a peptide bond. as Dr. Wolf's CHM 424 27- 99 Alanine and Glycine H + H3N C CH3 Dr. Wolf's CHM 424 O C H – O + H3N C O C – O H 27- 100 Alanylglycine + H3N H C CH3 O C H N C H O C – O H Two α-amino acids are joined by a peptide bond Two -amino in alanylglycine. It is a dipeptide. dipeptide Dr. Wolf's CHM 424 27- 101 Alanylglycine + H3N N-terminus H C CH3 O C H N C H H Ala—Gly O C – O C-terminus AG Dr. Wolf's CHM 424 27- 102 Alanylglycine and glycylalanine are Alanylglycine constitutional isomers constitutional + H3N H C O C + H3N C N C H CH3 H H H Dr. Wolf's CHM 424 C – O Alanylglycine Ala—Gly AG – O Glycylalanine Gly—Ala GA H O C O H N C O C H CH3 27- 103 Alanylglycine + H3N H C CH3 O C H N C H O C – O H The peptide bond is The characterized by a planar geometry. planar Dr. Wolf's CHM 424 27- 104 Higher Peptides Peptides are classified according to the number Peptides of amino acids linked together. of dipeptides, tripeptides, tetrapeptides, etc. Leucine enkephalin is an example of a Leucine pentapeptide. pentapeptide. Dr. Wolf's CHM 424 27- 105 Leucine Enkephalin Tyr—Gly—Gly—Phe—Leu YGGFL Dr. Wolf's CHM 424 27- 106 Oxytocin 3 2 4 5 Ile—Gln—Asn Tyr 1 Cys N-terminus C-terminus Cys—Pro—Leu—GlyNH2 S S 6 7 8 9 Oxytocin is a cyclic nonapeptide. Instead of having its amino acids linked in an Instead extended chain, two cysteine residues are joined by an S—S bond. bond. Dr. Wolf's CHM 424 27- 107 Oxytocin S—S bond An S—S bond between two cysteines is often referred to as a disulfide bridge. often disulfide Dr. Wolf's CHM 424 27- 108 27.8 Introduction to Peptide Introduction Structure Determination Structure Dr. Wolf's CHM 424 27- 109 Primary Structure The primary structure is the amino acid The sequence plus any disulfide links. sequence Dr. Wolf's CHM 424 27- 110 Classical Strategy (Sanger) 1. Determine what amino acids are present and Determine their molar ratios. their 2. Cleave the peptide into smaller fragments, 2. and determine the amino acid composition of these smaller fragments. these 3. Identify the N-terminus and C-terminus in the 3. parent peptide and in each fragment. parent 4. Organize the information so that the Organize sequences of small fragments can be overlapped to reveal the full sequence. overlapped Dr. Wolf's CHM 424 27- 111 27.9 Amino Acid Analysis Dr. Wolf's CHM 424 27- 112 Amino Acid Analysis Acid-hydrolysis of the peptide (6 M HCl, 24 hr) Acid-hydrolysis gives a mixture of amino acids. gives The mixture is separated by ion-exchange The chromatography, which depends on the differences in pI among the various amino acids. differences Amino acids are detected using ninhydrin. 7 Automated method; requires only 10-5 to 10--7 g of peptide. of Dr. Wolf's CHM 424 27- 113 27.10 Partial Hydrolysis of Proteins Dr. Wolf's CHM 424 27- 114 Partial Hydrolysis of Peptides and Proteins Acid-hydrolysis of the peptide cleaves all of the Acid-hydrolysis peptide bonds. peptide Cleaving some, but not all, of the peptide bonds Cleaving gives smaller fragments. gives These smaller fragments are then separated These and the amino acids present in each fragment determined. determined. Enzyme-catalyzed cleavage is the preferred Enzyme-catalyzed method for partial hydrolysis. method Dr. Wolf's CHM 424 27- 115 Partial Hydrolysis of Peptides and Proteins The enzymes that catalyze the hydrolysis of The peptide bonds are called peptidases, proteases, peptidases proteases or proteolytic enzymes. proteolytic enzymes Dr. Wolf's CHM 424 27- 116 Trypsin Trypsin is selective for cleaving the peptide bond Trypsin to the carboxyl group of lysine or arginine. to O O O NHCHC NHCHC NHCHC R R' R" lysine or arginine Dr. Wolf's CHM 424 27- 117 Chymotrypsin Chymotrypsin is selective for cleaving the peptide bond to the carboxyl group of amino acids with an aromatic side chain. O O O NHCHC NHCHC NHCHC R R' R" phenylalanine, tyrosine, tryptophan Dr. Wolf's CHM 424 27- 118 Carboxypeptidase Carboxypeptidase is selective for cleaving the peptide bond to the C-terminal amino acid. O O + H3NCHC R Dr. Wolf's CHM 424 protein C O – NHCHCO R 27- 119 27.11 End Group Analysis Dr. Wolf's CHM 424 27- 120 End Group Analysis Amino sequence is ambiguous unless we know Amino whether to read it left-to-right or right-to-left. whether We need to know what the N-terminal and Cterminal amino acids are. The C-terminal amino acid can be determined The by carboxypeptidase-catalyzed hydrolysis. by Several chemical methods have been Several developed for identifying the N-terminus. They depend on the fact that the amino N at the terminus is more nucleophilic than any of the amide nitrogens. amide Dr. Wolf's CHM 424 27- 121 Sanger's Method The key reagent in Sanger's method for The identifying the N-terminus is 1-fluoro-2,4identifying dinitrobenzene. 1-Fluoro-2,4-dinitrobenzene is very reactive 1-Fluoro-2,4-dinitrobenzene toward nucleophilic aromatic substitution (Section 23.5). (Section NO2 O2N Dr. Wolf's CHM 424 F 27- 122 Sanger's Method 1-Fluoro-2,4-dinitrobenzene reacts with the 1-Fluoro-2,4-dinitrobenzene amino nitrogen of the N-terminal amino acid. amino NO2 O2N O O F + H2NCHC NHCHC NHCH2C CH(CH3)2 NO2 O2N Dr. Wolf's CHM 424 O O NHCHC CH(CH3)2 O NHCH2C CH2C6H5 – NHCHCO CH3 CH2C6H5 NHCHC O O O – NHCHCO CH3 27- 123 Sanger's Method Acid hydrolysis cleaves all of the peptide bonds Acid leaving a mixture of amino acids, only one of which (the N-terminus) bears a 2,4-DNP group. which NO2 O O O + + O + NHCHCOH + H3NCHCO– + H3NCH2CO– + H3NCHCO– O2N CH3 CH2C6H5 CH(CH3)2 H3O+ NO2 O2N Dr. Wolf's CHM 424 O O NHCHC NHCHC CH(CH3)2 O NHCH2C CH2C6H5 O – NHCHCO CH3 27- 124 27.12 Insulin Dr. Wolf's CHM 424 27- 125 Insulin Insulin is a polypeptide with 51 amino acids. It has two chains, called the A chain (21 amino It acids) and the B chain (30 amino acids). acids) The following describes how the amino acid The sequence of the B chain was determined. sequence Dr. Wolf's CHM 424 27- 126 The B Chain of Bovine Insulin Phenylalanine (F) is the N terminus. Pepsin-catalyzed hydrolysis gave the four peptides: FVNQHLCGSHL FVNQHLCGSHL VGAL VCGERGF YTPKA Dr. Wolf's CHM 424 27- 127 The B Chain of Bovine Insulin FVNQHLCGSHL VGAL VCGERGF YTPKA Dr. Wolf's CHM 424 27- 128 The B Chain of Bovine Insulin Phenylalanine (F) is the N terminus. Pepsin-catalyzed hydrolysis gave the four peptides: FVNQHLCGSHL VGAL VCGERGF YTPKA Overlaps between the above peptide sequences were Overlaps found in four additional peptides: found SHLV LVGA ALT TLVC Dr. Wolf's CHM 424 27- 129 The B Chain of Bovine Insulin FVNQHLCGSHL SHLV LVGA VGAL ALT TLVC VCGERGF YTPKA Dr. Wolf's CHM 424 27- 130 The B Chain of Bovine Insulin Phenylalanine (F) is the N terminus. Pepsin-catalyzed hydrolysis gave the four peptides: FVNQHLCGSHL VGAL VCGERGF YTPKA Overlaps between the above peptide sequences were Overlaps found in four additional peptides: found SHLV LVGA ALT TLVC Trypsin-catalyzed hydrolysis gave GFFYTPK which Trypsin-catalyzed completes the sequence. completes Dr. Wolf's CHM 424 27- 131 The B Chain of Bovine Insulin FVNQHLCGSHL SHLV LVGA VGAL ALT TLVC VCGERGF GFFYTPK YTPKA Dr. Wolf's CHM 424 27- 132 The B Chain of Bovine Insulin FVNQHLCGSHL SHLV LVGA VGAL ALT TLVC VCGERGF GFFYTPK YTPKA FVNQHLCGSHLVGALTLVCGERGFFYTPKA Dr. Wolf's CHM 424 27- 133 Insulin The sequence of the A chain was determined The using the same strategy. using Establishing the disulfide links between cysteine Establishing residues completed the primary structure. residues Dr. Wolf's CHM 424 27- 134 Primary Structure of Bovine Insulin N terminus terminus of A chain chain S S C terminus terminus of A chain chain 15 5 EQC CS L YQL 20 FIV EN C YC S ASV 10 N S S QHL S FVN C 5 GS H L VG A L YL V C 20 15 10 G N terminus terminus E of B chain of FG R TYF AKP C terminus terminus 25 of B chain chain 30 Dr. Wolf's CHM 424 27- 135 27.13 The Edman Degradation and The Automated Sequencing of Peptides Peptides Dr. Wolf's CHM 424 27- 136 Edman Degradation 1. Method for determining N-terminal amino 1. acid. acid. 2. Can be done sequentially one residue at a Can time on the same sample. Usually one can determine the first 20 or so amino acids from the N-terminus by this method. the 10 3. 10--10 g of sample is sufficient. of 4. Has been automated. Dr. Wolf's CHM 424 27- 137 Edman Degradation The key reagent in the Edman degradation is The phenyl isothiocyanate. phenyl N Dr. Wolf's CHM 424 C S 27- 138 Edman Degradation Phenyl isothiocyanate reacts with the amino Phenyl nitrogen of the N-terminal amino acid. nitrogen O C6H5N C S Dr. Wolf's CHM 424 + + H3NCHC R NH peptide 27- 139 Edman Degradation S O C6H5NHCNHCHC peptide NH R O C6H5N C S Dr. Wolf's CHM 424 + + H3NCHC R NH peptide 27- 140 Edman Degradation S O C6H5NHCNHCHC NH peptide R The product is a phenylthiocarbamoyl (PTC) derivative. The PTC derivative is then treated with HCl in The an anhydrous solvent. The N-terminal amino acid is cleaved from the remainder of the peptide. peptide. Dr. Wolf's CHM 424 27- 141 Edman Degradation S O C6H5NHCNHCHC peptide NH R HCl S C6H5NH C C N Dr. Wolf's CHM 424 CH R O + + H3N peptide 27- 142 Edman Degradation The product is a thiazolone. Under the conditions of its formation, the thiazolone rearranges to a phenylthiohydantoin (PTH) derivative. S C6H5NH C C N Dr. Wolf's CHM 424 CH R O + + H3N peptide 27- 143 Edman Degradation C6H5 S N C C The PTH derivative is The isolated and identified. The remainder of the peptide is subjected to a second Edman degradation. degradation. O CH HN R S C6H5NH C C N Dr. Wolf's CHM 424 CH R O + + H3N peptide 27- 144 27.14 The Strategy of Peptide Synthesis Dr. Wolf's CHM 424 27- 145 General Considerations Making peptide bonds between amino acids is Making not difficult. not The challenge is connecting amino acids in the The correct sequence. correct Random peptide bond formation in a mixture of Random phenylalanine and glycine, for example, will give phenylalanine glycine for four dipeptides. four Phe—Phe Gly—Gly Phe—Gly Gly—Phe Gly Gly Phe Dr. Wolf's CHM 424 27- 146 General Strategy 1. Limit the number of possibilities by Limit "protecting" the nitrogen of one amino acid and the carboxyl group of the other. and N-Protected phenylalanine O X NHCHCOH CH2C6H5 Dr. Wolf's CHM 424 C-Protected glycine O H2NCH2C Y 27- 147 General Strategy 2. Couple the two protected amino acids. O NHCHC X O NHCH2C Y CH2C6H5 O X NHCHCOH CH2C6H5 Dr. Wolf's CHM 424 O H2NCH2C Y 27- 148 General Strategy 3. Deprotect the amino group at the N-terminus Deprotect and the carboxyl group at the C-terminus. and O X O NHCHC NHCH2C Y CH2C6H5 O + H3NCHC Dr. Wolf's CHM 424 O – NHCH2CO CH2C6H5 Phe-Gly 27- 149 27.15 Amino Group Protection Dr. Wolf's CHM 424 27- 150 Protect Amino Groups as Amides Amino groups are normally protected by Amino converting them to amides. converting Benzyloxycarbonyl (C6H5CH2O—) is a common O—) protecting group. It is abbreviated as Z. Z-protection is carried out by treating an amino -protection acid with benzyloxycarbonyl chloride. acid Dr. Wolf's CHM 424 27- 151 Protect Amino Groups as Amides O O CH2OCCl CH + + – H3NCHCO CH2C6H5 1. NaOH, H2O 2. H+ O CH2OC CH Dr. Wolf's CHM 424 O NHCHCOH CH2C6H5 (82-87%) 27- 152 Protect Amino Groups as Amides O CH2OC CH O NHCHCOH CH2C6H5 iis abbreviated as: s O ZNHCHCOH or Z-Phe CH2C6H5 Dr. Wolf's CHM 424 27- 153 Removing Z-Protection An advantage of the benzyloxycarbonyl An protecting group is that it is easily removed by: protecting a) hydrogenolysis b) cleavage with HBr in acetic acid Dr. Wolf's CHM 424 27- 154 Hydrogenolysis of Z-Protecting Group O CH2OC CH O NHCHCNHCH2CO2CH2CH3 CH2C6H5 H2, Pd O CH3 CH Dr. Wolf's CHM 424 CO2 H2NCHCNHCH2CO2CH2CH3 CH2C6H5 (100%) 27- 155 HBr Cleavage of Z-Protecting Group O CH2OC CH O NHCHCNHCH2CO2CH2CH3 CH2C6H5 HBr O CH2Br CH Dr. Wolf's CHM 424 CO2 + H3NCHCNHCH2CO2CH2CH3 – CH2C6H5 Br (82%) 27- 156 The tert-Butoxycarbonyl Protecting Group The tertO (CH3)3COC O NHCHCOH CH2C6H5 iis abbreviated as: s O BocNHCHCOH Boc or Boc-Phe CH2C6H5 Dr. Wolf's CHM 424 27- 157 HBr Cleavage of Boc-Protecting Group O (CH3)3COC O NHCHCNHCH2CO2CH2CH3 CH2C6H5 HBr O H3C C CH2 H3C Dr. Wolf's CHM 424 CO2 + H3NCHCNHCH2CO2CH2CH3 – CH2C6H5 Br (86%) 27- 158 27.16 Carboxyl Group Protection Dr. Wolf's CHM 424 27- 159 Protect Carboxyl Groups as Esters Carboxyl groups are normally protected as Carboxyl esters. esters. Deprotection of methyl and ethyl esters is by hydrolysis in base. Benzyl esters can be cleaved by hydrogenolysis. Dr. Wolf's CHM 424 27- 160 Hydrogenolysis of Benzyl Esters O O C6H5CH2OC O NHCHCNHCH2COCH2C6H5 CH2C6H5 H2, Pd O C6H5CH3 CO2 Dr. Wolf's CHM 424 + – H3NCHCNHCH2CO CH2C6H5 (87%) CH3C6H5 27- 161 27.17 Peptide Bond Formation Dr. Wolf's CHM 424 27- 162 Forming Peptide Bonds The two major methods are: 1. coupling of suitably protected amino acids 1. using N,N'-dicyclohexylcarbodiimide (DCCI) 2. via an active ester of the N-terminal amino 2. active acid. acid. Dr. Wolf's CHM 424 27- 163 DCCI-Promoted Coupling O O ZNHCHCOH + H2NCH2COCH2CH3 CH2C6H5 DCCI, chloroform O ZNHCHC O NHCH2COCH2CH3 CH2C6H5 Dr. Wolf's CHM 424 (83%) 27- 164 Mechanism of DCCI-Promoted Coupling O + ZNHCHCOH C6H11N C NC6H11 CH2C6H5 H C6H11N O C C6H11N Dr. Wolf's CHM 424 OCCHNHZ CH2C6H5 27- 165 Mechanism of DCCI-Promoted Coupling The species formed by addition of the Zprotected amino acid to DCCI is similar in protected structure to an acid anhydride and acts as an acylating agent. acylating Attack by the amine function of the carboxylprotected amino acid on the carbonyl group protected leads to nucleophilic acyl substitution. leads H C6H11N O C C6H11N Dr. Wolf's CHM 424 OCCHNHZ CH2C6H5 27- 166 Mechanism of DCCI-Promoted Coupling O H C6H11N C O+ ZNHCHC O NHCH2COCH2CH3 CH2C6H5 C6H11NH O H2NCH2COCH2CH3 H C6H11N O C C6H11N Dr. Wolf's CHM 424 OCCHNHZ CH2C6H5 27- 167 The Active Ester Method A p-nitrophenyl ester is an example of an "active -nitrophenyl ester." ester." p-Nitrophenyl is a better leaving group than -Nitrophenyl methyl or ethyl, and p-nitrophenyl esters are -nitrophenyl more reactive in nucleophilic acyl substitution. more Dr. Wolf's CHM 424 27- 168 The Active Ester Method O O ZNHCHCO NO2 + NO H2NCH2COCH2CH3 CH2C6H5 chloroform O ZNHCHC O NHCH2COCH2CH3 + HO CH2C6H5 Dr. Wolf's CHM 424 (78%) NO2 NO 27- 169 27.18 Solid-Phase Peptide Synthesis: The Merrifield Method Dr. Wolf's CHM 424 27- 170 Solid-Phase Peptide Synthesis In solid-phase synthesis, the starting material is In bonded to an inert solid support. bonded Reactants are added in solution. Reaction occurs at the interface between the Reaction solid and the solution. Because the starting material is bonded to the solid, any product from the starting material remains bonded as well. the Purification involves simply washing the Purification byproducts from the solid support. byproducts Dr. Wolf's CHM 424 27- 171 The Solid Support CH2 CH CH2 CH CH2 CH CH2 CH The solid support is a copolymer of styrene and The divinylbenzene. It is represented above as if it were polystyrene. Cross-linking with divinylbenzene simply provides a more rigid polymer. polymer. Dr. Wolf's CHM 424 27- 172 The Solid Support CH2 CH CH2 CH CH2 CH CH2 CH Treating the polymeric support with Treating chloromethyl methyl ether (ClCH2OCH3) and chloromethyl and SnCl4 places ClCH2 side chains on some of the SnCl ClCH benzene rings. benzene Dr. Wolf's CHM 424 27- 173 The Solid Support CH2 CH CH2 CH CH2 CH CH2 CH CH2Cl CH The side chain chloromethyl group is a benzylic The halide, reactive toward nucleophilic substitution (SN2). (S Dr. Wolf's CHM 424 27- 174 The Solid Support CH2 CH CH2 CH CH2 CH CH2 CH CH2Cl CH The chloromethylated resin is treated with the Bocprotected C-terminal amino acid. Nucleophilic protected substitution occurs, and the Boc-protected amino acid is bound to the resin as an ester. acid Dr. Wolf's CHM 424 27- 175 The Merrifield Procedure CH2 CH CH2 CH CH2 O – BocNHCHCO CH CH2 CH CH2Cl CH R Dr. Wolf's CHM 424 27- 176 The Merrifield Procedure CH2 CH CH2 CH CH2 O CH CH2 CH CH2 CH BocNHCHCO Next, the Boc Next, protecting group is removed with HCl. removed Dr. Wolf's CHM 424 R 27- 177 The Merrifield Procedure CH2 CH CH2 CH CH2 O CH CH2 CH CH2 CH H2NCHCO DCCI-promoted DCCI-promoted coupling adds the second amino acid second Dr. Wolf's CHM 424 R 27- 178 The Merrifield Procedure CH2 CH CH2 CH CH2 O BocNHCHC R' Dr. Wolf's CHM 424 CH O CH2 CH CH2 CH NHCHCO R Remove the Boc Remove protecting group. protecting 27- 179 The Merrifield Procedure CH2 CH CH2 CH CH2 O H2NCHC R' Dr. Wolf's CHM 424 CH O CH2 CH CH2 CH NHCHCO R Add the next amino Add acid and repeat. acid 27- 180 The Merrifield Procedure CH2 CH CH2 O CH O + H3N peptide C NHCHC R' Dr. Wolf's CHM 424 CH2 CH O CH2 CH CH2 CH NHCHCO R Remove the peptide Remove from the resin with HBr in CF3CO2H HBr 27- 181 The Merrifield Procedure CH2 CH CH CH2 O CH O + H3N peptide C NHCHC R' Dr. Wolf's CHM 424 CH2 O CH CH2 CH CH2Br CH – NHCHCO R 27- 182 The Merrifield Method Merrifield automated his solid-phase method. Synthesized a nonapeptide (bradykinin) in 1962 Synthesized in 8 days in 68% yield. in Synthesized ribonuclease (124 amino acids) in Synthesized 1969. 1969. 369 reactions; 11,391 steps Nobel Prize in chemistry: 1984 Dr. Wolf's CHM 424 27- 183 27.19 Secondary Structures of Peptides and Proteins Dr. Wolf's CHM 424 27- 184 Levels of Protein Structure Primary structure = the amino acid sequence Primary plus disulfide links plus Secondary structure = conformational Secondary relationship between nearest neighbor amino acids acids α helix helix pleated β sheet pleated Dr. Wolf's CHM 424 27- 185 Levels of Protein Structure The α-helix and pleated β sheet are both The -helix characterized by: characterized planar geometry of peptide bond anti conformation of main chain hydrogen bonds between N—H and O=C Dr. Wolf's CHM 424 27- 186 Pleated β Sheet Pleated Shown is a β sheet of protein chains composed of Shown alternating glycine and alanine residues. alternating Adjacent chains are antiparallel. Hydrogen bonds between chains. van der Waals forces produce pleated effect. Dr. Wolf's CHM 424 27- 187 Pleated β Sheet Pleated β Sheet is most commonly seen with amino acids having small side chains (glycine, alanine, serine). having 80% of fibroin (main protein in silk) is repeating 80% sequence of —Gly—Ser—Gly—Ala—Gly—Ala—. sequence β Sheet is flexible, but resists stretching. Sheet Dr. Wolf's CHM 424 27- 188 α Helix Helix Shown is an α helix of a protein Shown in which all of the amino acids are L-alanine. Helix is right-handed with 3.6 Helix amino acids per turn. amino Hydrogen bonds are within a Hydrogen single chain. single Protein of muscle (myosin) and Protein wool (α-keratin) contain large wool -keratin) regions of α-helix. Chain can -helix. be stretched. be Dr. Wolf's CHM 424 27- 189 27.20 Tertiary Structure of Peptides and Proteins Dr. Wolf's CHM 424 27- 190 Tertiary Structure Refers to overall shape (how the chain is folded) Fibrous proteins (hair, tendons, wool) have Fibrous elongated shapes elongated Globular proteins are approximately spherical most enzymes are globular proteins an example is carboxypeptidase Dr. Wolf's CHM 424 27- 191 Carboxypeptidase Carboxypeptidase is an enzyme that catalyzes Carboxypeptidase the hydrolysis of proteins at their C-terminus. the It is a metalloenzyme containing Zn2+ at its active site. active An amino acid with a positively charged side An chain (Arg-145) is near the active site. chain Dr. Wolf's CHM 424 27- 192 Carboxypeptidase Disulfide bond Zn2+ Arg-145 N-terminus C-terminus tube model Dr. Wolf's CHM 424 ribbon model 27- 193 What happens at the active site? + H3N •• • O• peptide C O NHCHC – R Dr. Wolf's CHM 424 O H2N +C Arg-145 H2N 27- 194 What happens at the active site? + H3N •• • O• peptide C O NHCHC – R O H2N +C Arg-145 H2N The peptide or protein is bound at the active site The by electrostatic attraction between its negatively charged carboxylate ion and arginine-145. charged Dr. Wolf's CHM 424 27- 195 What happens at the active site? + H3N •• • O• peptide C Zn2+ O NHCHC – R O H2N +C Arg-145 H2N Zn2+ acts as a Lewis acid toward the carbonyl Zn oxygen, increasing the positive character of the carbonyl carbon. carbonyl Dr. Wolf's CHM 424 27- 196 What happens at the active site? + H3N Zn2+ •• • O• peptide C O NHCHC – R O H2N +C Arg-145 H2N H • O• •• H Water attacks the carbonyl carbon. Nucleophilic acyl substitution occurs. acyl Dr. Wolf's CHM 424 27- 197 What happens at the active site? Zn2+ H2N + H3N •• • O• peptide C +C •• – O• • •• H2N O + H3NCHC – R Dr. Wolf's CHM 424 Arg-145 O 27- 198 27.21 Coenzymes Dr. Wolf's CHM 424 27- 199 Coenzymes The range of chemical reactions that amino acid The side chains can participate in is relatively limited. limited. acid-base (transfer and accept protons) nucleophilic acyl substitution Many other biological processes, such as Many oxidation-reduction, require coenzymes, coenzymes cofactors, or prosthetic groups in order to occur. cofactors or prosthetic groups Dr. Wolf's CHM 424 27- 200 Coenzymes NADH, coenzyme A and coenzyme B12 are examples of coenzymes. examples Heme is another example. Dr. Wolf's CHM 424 27- 201 Heme H2C CH H3C CH3 N N CH CH2 Fe H3C N HO2CCH2CH2 N CH3 CH2CH2CO2H Molecule surrounding iron is a Molecule type of porphyrin. type Dr. Wolf's CHM 424 27- 202 Myoglobin C-terminus Heme N-terminus Heme is the coenzyme that binds oxygen in myoglobin Heme (oxygen storage in muscles) and hemoglobin (oxygen transport). transport). Dr. Wolf's CHM 424 27- 203 27.22 Protein Quaternary Structure: Hemoglobin Dr. Wolf's CHM 424 27- 204 Protein Quaternary Structure Some proteins are assemblies of two or more Some chains. The way in which these chains are organized is called the quaternary structure. organized Hemoglobin, for example, consists of 4 Hemoglobin, subunits. subunits. There are 2 α chains (identical) and 2 β chains There (also identical). (also Each subunit contains one heme and each Each protein is about the size of myoglobin. Dr. Wolf's CHM 424 27- 205 End of Chapter 27 Dr. Wolf's CHM 424 27- 206 ...
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This document was uploaded on 01/03/2012.

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