Unformatted text preview: Protein Biochemistry : A Brief Introduction
Dr. Mohamad Sadikin DSc Department of Biochemistry and Molecular Biology FKUI The origin of the protein name is a Greek word (proteos), means the first, the most important or the most eminent based on the fact : the substances is the most abundant compound found in any dried living matter or cell (the 2nd after water) logically, the most abundant compound should have the most important function The importance of prot. roles in realising 3 most basic life signs, compared to other macromolecules can be seen in the next table Movement Multiplicat Gradient ion Lipids Nucleic acid Polysachar ide Protein (-) (-) (-) (+) (-) (+) (+) (+) (+) (-) (-) (+) Other life signs or functions can be added as much as we will, But practically for whatsoever life function there will be practically at least one protein corresponding to each function Life functions may be very different each other: structural function is passive, whereas metabolism or movement is very active one Very important question : how a type of molecule can support and carry out very different, even contradictory functions (active vs passive) ? The phenomenon can not be explained solely by the size of protein molecule (a macromolecule) DNA (a nucleic acid) is the largest macromolecule in the cell, but DNA carries out only 1 function The explication should be looked for in the shape of the protein If this is the case, the question must be reformulated and sharpened : how a protein, as a macromolecule, but not the other macromolecule, could take a great variety of shape as reflected by its functions ? The answer must be searched in the nature of protein molecule itself Definition : protein is heteropolymer of amino acids, bound each other by peptidic bond, occupe their strict position and all are the results of the expression of information contained in gene (information unit in the genome or all the DNA strand)
Key words : heteropolymer, amino acid, peptidic bond, gene expression Amino acid
Amino acid is an organic compound posessing an acid as well as a basic group (NH2) in its molecule But not every any amino acid can form a protein, a protein forming amino acid must fulfill the following criteria : 1.The acid moeity must be a carboxylic group Consequently, any aa whose acid group is not carboxylic one,i.e sulfate (as in taurin) will never be found in whatever protein 2.The carboxylic and the amino groups must be bound to a same C atom : C a protein forming aa has to be an -aa an aa other than -aa is excluded A general structure of an -aa : H 2HN-C -COOH R As C is an asymmetric C atom (because it binds 4 different atom or groups), any -aa can be exist in 2 stereoisomer or configuration : either L or D 3.Only L-aa can form a protein But there a number of L -aa, metabolically very important, who are never found any protein (i.e citruline and ornithin) 4.A L-aa can form and be found in any protein, if and only if the aa has a specific genetic sign in gene, named as codon (gene itself can be considered as an information unit in a DNA molecule or genom Any codon code only 1 aa, however the reverse statement is not true : any protein forming aa may have > 1 codon Until now it is known that there are only 20 aa found to build any protein from various source of life being (from bacteria or even from virus to human) This is a very extraordinary phenomenon : one of some universalities in life being (2 others are universality of genetic letter or codon and in ATP as energy currency) what is valid for virus or bacteria, is valid also for human. Amino Acid Classification Despite its relatively few types, it is more aa must be classified for the convenience of our understanding There 2 ways to classiffy protein forming aa : 1.According to capability of our body to synthetize any given aa 2.According to physicochemical nature of R groups The capability of the body to synthesize aa : 2 groups of aa : 1.Essentials aa 2.Nonessentials aa Essentials aa : an aa is considered essential if it can not be synthetized by the body it must be supplied by the food Nonessentials aa : all the aa that can be synthesized by the body it does not net be in the food Note: nonessentials aa does not mean not important. Both groups are important Peptidic bond
There several possibilities to bind an aa to another aa : - By an acid anhydridic bond - By a hydrazidic bond - By a peptidic bond Peptidic bond is much more stable than 2 other bond Peptidic bond can also be prolonged practically infinitely In reality, to form a protein, aa are bound each other only by peptidic bond It can be said that peptidic bond is the backbone of every protein, whereas the aminoacids are its building blocks Chemically, a peptidic bond is : Analogue to an esther bond (instead of OH, it is NH2 which form covalent bond with COOH) Formed as a condensation of a NH2 group of a molecule of an aa with a COOH group of another molecule of an aa by removing a water (H2O) from both groups Formation of a peptidic bond : H H R1-C-COOH + R2-C-COOH NH2 NH2 H OHH R1-C-C-N-C-COOH + H2O NH2 R2 Organization of a protein molecule A protein is not only composed of a well arranged of aa in a certain sequence It is also build by interaction of various gtoups found in constituent aa such as CO (found as part of peptidic bond), -NH (also part of peptidic bond), and various form of R group (acidic, basic, hydophylic and hydrophobic) The interactions obey physical rule : 1.Same charge repel each other 2.Opposite charge attract each other 3.Hydrophobic moieties aggregate each other and avoid water and hydrophilic molecules or moieties. Results : - Various geometric pattern in segment or part of polypeptide / protein molecule (secondary structure) as well as in the whole molecule itself (tertiary structure) - The primary structure is the arrangement of aa in a protein Note: The sole determinant of primary str (aa sequence) is the gene. once it is formed, it can not be changed any more - Only change in gene can change 1 aa on a protein mutation On the other hand, the higher structures are very susceptible to the environtment variations, especially pH & to : - Any change in 1 or more environtment factors modify the higher structure - The higher str is easier to be changed by environtment than the lower str Biological function of any protein is determined by the 3 D strt (tertiary str) Change in 3 D str must disturb the biological function of the protein denaturation : loss of 3D str (=tertiary str or conformation) is the result of any env modif (pH,to, organic solvent, heavy metals such Pb, Cd, Hg etc, uv or x-ray or even any simple physical treatment as fort shaking) and always conduct to decrease or even loss of specific biological activity or function of the protein. More severe denaturation result in decrease of the protein solubility. *Geometric forms of secondary structures : As a result of the interactions between various R group of adjacent aa, some geometric str will be formed locally (in a segment) or in the whole molecule It is well known that there are 5 geometric form in the secnd strc : - -helix - -sheet - Loop - Bent - Random coil * Geometric forms of the global structure (3 D or tertiary structure) of protein : There are only 2 Each 3 D strc indicates the general function of any protein. The 3 D str: - Globular globular protein : proteins whose ratio horizontal axe : vertical axe are between 1 - 2 - Fibrous protein : the ratio are >10 - Generally, globular proteins are regulator protein (enzyme,mediator,transporter etc) - Fibrous proteins are structural or supporter protein (collagen,keratin etc) Relations among the various str : - If a protein has > 1 secondary structure, then it is a globular protein. Consequently, it is regulator protein - On the contrary, if it is consisted only of 1 secondary protein, then it is a fibrous protein. Consequently, it is a structural or support protein - Change in 1 aa (primary str) will change the local interaction berween adjacent R group change in second str tertiary str perturbation or even loss of biologisal (i.e. in sickle cell anemia) ...
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