MLBGCC2 1 CBCS STRUCTURE Basics of biomolecules 42

MLB-G-CC-2 -1 (CBCS STRUCTURE) Basics of biomolecules (4+2 = 6 credits) SEMESTER – 2 MLB-G-CC-2 -1 -TH (4 credits/50 marks) Unit 4 Proteins No. of Hours: 10 Amino acids: structure of twenty amino acids, classification, titration curve of amino acids, concept of zwitterionic structure, physical and chemical properties. (8 hours) Proteins: classification of proteins on the basis of composition, conformation and function, different level of structural organization of proteins(primary, secondary, tertiary & quaternary), forces stabilizing protein structure and shape, physical and chemical properties. Domains and Motifs, Role of weak forces in biology (10 hours)

Amino Acids are the building units of proteins. Proteins are polymers of amino acids linked together by “ Peptide bond” q There about 300 amino acids occur in nature. Only 20 of them occur in proteins. Structure of amino acids: Each amino acid has 4 different groups attached to α- carbon (which is Catom next to COOH). These 4 groups are : amino group, COOH gp, Hydrogen atom and side Chain ( R group) R

Amino Acids • While their name implies that amino acids are compounds that contain an —NH 2 group and a —COOH group, these groups are actually present as —NH 3+ and —COO– respectively. • They are classified as , b, g, etc. amino acids according the carbon that bears the nitrogen.

The 20 (22) Key Amino Acids • More than 700 amino acids occur naturally, but 20 (22)of them are especially important. • These 22 amino acids are the building blocks of proteins. • They take part in translation • All are -amino acids. • They differ in respect to the (R) group attached to the carbon.

Selenocysteine is the 21 st amino acid that naturally occur in proteins in all three domains of life, but not in every lineage. Selenocysteine is a cysteine analogue and acts as a building block of selenoproteins. Selenocysteine is present in several enzymes.

Pyrrolysine, encoded by the 'amber’ stop codon (UAG) is an amino acid that is used in the biosynthesis of proteins in some methanogenic archea and eubacteria. Pyrrolysine is not present in humans

Redefinition of Codons

• At physiological PH (7. 4), -COOH gp is dissociated forming a negatively charged carboxylate ion (COO-) and amino gp is protonated forming positively charged ion (NH 3+) forming Zwitter ion • N. B. Proline is an imino acid not amino acid Classification of amino acids

Properties of Glycine solubility: soluble in water; not soluble in nonpolar solvent more consistent with this • • O • • + – • • H 3 NCH 2 C O • • than this • • O • • H 2 NCH 2 C OH • •

Properties of Glycine more consistent with this • • O • • + – • • H 3 NCH 2 C O • • called a zwitterion or dipolar ion

Acid-Base Properties of Glycine • The zwitterionic structure of glycine also follows from considering its acid-base properties. • A good way to think about this is to start with the structure of glycine in strongly acidic solution, say p. H = 1. • At p. H = 1, glycine exists in its protonated form (a monocation). • • O • • + H 3 NCH 2 C • • OH • •

Acid-Base Properties of Glycine • As the p. H is raised, which is 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? • One can choose between them by estimating their respective p. Kas. typical ammonium ion: p. Ka ~9 • • O • • + H 3 NCH 2 C • • OH • • typical carboxylic acid: p. Ka ~5

Acid-Base Properties of Glycine • The more acidic proton belongs to the COOH group. It is the first one removed as the p. H is raised. • • O • • + H 3 NCH 2 C • • OH • • typical carboxylic acid: p. Ka ~5

Acid-Base Properties of Glycine • Therefore, the more stable neutral form of glycine is the zwitterion. • • O • • + H 3 NCH 2 C – • • • O • • • O • • + H 3 NCH 2 C • • OH • • typical carboxylic acid: p. Ka ~5

Acid-Base Properties of Glycine • The measured p. Ka of glycine is 2. 34. • Glycine is stronger than a typical carboxylic acid because the positively charged N acts as an electron-withdrawing, acidstrengthening substituent on the carbon. • • O • • + H 3 NCH 2 C • • OH • • typical carboxylic acid: p. Ka ~5

Acid-Base Properties of Glycine A proton attached to N in the zwitterionic form of nitrogen can be removed as the p. H is increased further. • • O • • + H 3 NCH 2 C – • • • O • • • HO – • • O • • H 2 NCH 2 C – • • • O • • The p. Ka for removal of this proton is 9. 60. This value is about the same as that for NH 4+

Isoelectric Point p. I • • O • • + H 3 NCH 2 C p. Ka = 2. 34 • • O • • + H 3 NCH 2 C p. Ka = 9. 60 • • O • • H 2 NCH 2 C • • OH • • • The p. H at which the concentration of the zwitterion is a maximum is called the isoelectric point. – • Its numerical value is • • O • • the average of the two • • p. Kas. – • The p. I of glycine is 5. 97. • • O • •

Titration curve of amino acids One -NH 2 group One –COOH group

One -NH 2 group One –COOH group

Physical Properties of Amino Acid 1. Solubility: Most of the amino acids are usually soluble in water, and insoluble in organic solvents. 2. Melting Point: Amino acids are generally melt at higher temperature of ten above 2000 C. 3. Taste: Amino acids may be sweet (Gly, Ala & Val), tasteless (Leu) or Bitter (Arg & Ile). 4. Optical Properties: All amino acids possess optical isomers due to the presence of asymmetric α-carbon atoms.

Chemical Properties of Amino Acid Chemical reactions of amino acids due to carboxyl and amino groups: Reaction due to carboxyl groups Reaction due to amino groups Reaction due to carboxyl and amino groups

Chemical Properties of Amino Acid Chemical reactions of amino acids due to carboxyl and amino groups: Reaction due to carboxyl groups a) Decarboxylation: Reaction due to amino groups a) Reaction with Formaldehyde b) Reaction with Benzaldehyde b) Reaction with Alkalies (Salt formation): c) Reaction with Alcohols (Esterification) : c) Reaction with Nitrous acid (Van slyke reaction): d) Reaction with Sanger’s Reagent d) Reaction with Amines: e) Reaction with DANSYL Chloride f) Reaction with acylating agents (Acylation):

Reaction due to carboxyl groups

Reaction due to amino groups

Reaction due to carboxyl and amino groups

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