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Characteristics of Aliphatic, Nonpolar R Groups
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• Hydrocarbon R groups• Gly has no side chain (H) (non-chiral)• Hydrophobic contacts• Not exposed in large numbers on the surface, except in proteins interacting with lipids• Ala used in mutagenesis studies bc of small inert side chain
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Leucine Zipper
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Aliphatic residue such as Leu or Ile repeated every 7 residues on helix. Acts as dimerization domain. Sequence: L(X6)I(X6)L(X6)L(X6). 7 residues ~ 2 turns of helix.
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Cysteine
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Polar, unchargedCysC
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Sickle Cell Anemia
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Mutation of the B-globin gene. Mutated hemoglobin tends to crystallize.
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Glutamate (Glutamic Acid)
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Negatively chargedGluE
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Lysine
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Positively chargedLysK
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Characteristics of Aromatic R Groups
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• Phe, Tyr, Trp absorb UV light at 280 nm. Used for protein detection and quantification. Allows each protein to be assigned an extinction coefficient.• Trp (W) has only one codon, largest AA, less frequent in protein
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Valine
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Nonpolar, aliphaticValV
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pol III
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small RNAs (tRNA, etc.)
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Proline
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Nonpolar, aliphaticProP
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Arginine
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Positively chargedArgR
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Vancomycin and B-Lactam Antibiotics
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Interfere with synthesis of cell wall
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Sulfonamide
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Interfere with DNA synthesis
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Erythromycin and tetracycline
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Disrupt ribosomes that make proteins
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E-F Hand Motif
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Calcium Binding
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Threonine
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Polar, unchargedThrT
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Quinolone
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Inhibit enzymes involved in replicating DNA
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Leucine
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Nonpolar, aliphaticLeuL
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Tryptophan
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AromaticTrpW
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Isoleucine
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Nonpolar, aliphaticIleI
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Histidine
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Positively charged, AromaticHisH
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Acidic Region
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Signaling domainInteraction domain
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Augmentin
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Combo drug of amoxicillin (B-lactam) and clavulinate (reversible inhibitor of B-lactamase)
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Post Translational Mods:Permanent
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Partial proteolysis – zymogens, insulin
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Hydrophobic region
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TransmembraneSignal peptideInteraction domain
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Alanine
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Nonpolar, aliphaticAlaA
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Regulatory Transcription Factors (
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control the rate of transcription function either as activators or repressors are often tissue-specific
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Amphipathic helix
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Hydrophobic AA line up on one side, hydrophilic on the other side. Often seen in membrane proteins
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Basal Transcription Factors (TFIIs)
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Locate TATA Box, define transcription start recruit RNA polymerase II provide low level of transcription present in all cell nuclei
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Alpha Helix
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Right handed coil3.6 residues per turnPitch is 5.4 angstromStabilized by hydrogen bondsAmino acid side faces out
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Post Translational Mods:Reversible (covalent additions)
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Phosphorylation of proteins via protein kinases: occurs on Ser/Thr or Tyr residues. Methylation of Lys and Arg of histones in regulation of gene transcription
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Asparagine
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Polar, unchargedAsnN
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Characteristics of Charged R Groups
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• Often protein surface• Intra- and inter- chain interactions• Salt bridges• Many enzymatic sites (bc can change ionization states)
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Glycosyl-phosphatidyl inositol anchor (GPI anchor)
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Addition of lipid• Added in lumen of the ER to a synthesized protein• Signal near the C-terminus of the protein. Precursor protein is cleaved before two small residues (w+1 and w+2) and transferred to the GPI• GPI anchored proteins:o - have more mobility on lipid membranes than transmembrane proteins.o - often accumulate in cholesterol-rich microdomains (membrane rafts).
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N-GlycosylationGlycosylation General
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The sequence Ser/Thr-X-Asn is the motif of the primary structure where N gets glycosylated. (X not a Proline)• during or immediately after protein synthesis.• occurs in the lumen of the endoplasmic reticulum• Glycoproteins are destined to be secreted or exposed on the cell surface.
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Characteristics of Polar R Groups
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• Hydroxyl, sulfhydryl, or carboxylamide • H-bonding• Cys in disulfide bonding• Pro has circular side chain, fixed dihedral angle provides rigidity (not polar in structure, but behaves as such in protein)• Asn (N) was first AA to be isolated
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Aspartate (Aspartic Acid)
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Negatively chargedAspD
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Pol II
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transcribing protein-coding genes
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Helix Loop Helix Motif
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DNA Binding
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Penicillin
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Reversibly inhibit the transpeptidase that catalyzes the crosslinking of a bacterial cell wall. Penicillin type drugs are B-lactam antibiotics. In the presence of B-lactamase (hydrolyzes B-lactams) bacteria are penicillin resistant.
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Kwashiorkor
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Protein-Energy Malnutrition (PEM) associated with Feet edema, distended abdomen, enlarged liver, dermatosis, tooth loss. Also associated with alfatoxin poisoning
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Bohr Effect
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The affinity of oxygen binding to hemoglobin is decreased by decreasing pH or increasing CO2 concentration (Bohr effect).
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Tyrosine
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AromaticTyrY
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Glutamine
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Polar, unchargedGlnQ
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Basic region
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Nuclear localization signalNucleic acid binding regionInteraction domain with glycosamioglycans
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Serine
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Polar, unchargedSerS
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Pol I
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making rRNA
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Glycine
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Nonpolar, aliphaticGlyG
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Essential Amino Acids
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Ingesting These Little Molecules Has Value When Knowledge Fails(Lys, Thr, Leu, Met, Ile, His, Phe, Val, Trp)
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Phenylalanine
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AromaticPheF
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Phenylketonuria (PKU)
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Conversion of Phe->Tyr by Phe-hydroxylase is deficient. Accumulation of Phe and its breakdown products in the blood result in mental retardation. Effects can be prevented. Treatment is low protein supplemented with AA mix low in Phe. Aspartame contains an ester of the Asp-Phe dipeptide.
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Methionine
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Nonpolar, aliphaticMetM
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Marasmus
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Protein-Energy Malnutrition (PEM) associated with emaciation, muscle-wasting, loss of adipose
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Post Translational Mods:Relatively permanent (covalent additions)
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Glycosylation - Ser/Thr (O-linked) and Asn (N-linked oligosaccharides) Hydroxylation - collagens Acylation, prenylation, methylation, addition of glycosyl-phosphatidyl-Inositol anchor ADP-ribosylation. Covalent prosthetic groups (e.g. biotin and phosphopanthetein for lipid synthesis)
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