Classification and Structure ofAmino Acid

By:- Vivek KumarVivek KumarProgramme:- Bs-Ms (Physics)School:- School Of Basic Sciences and Researches

[1] Amino Acids

(1) Description The “standard” amino acids are -amino acids.‒ primary amino group (NH2)‒ carboxylic acid group (COOH)

Proline is an exception with a secondary amino group, but, it is still referred to as an -amino acid.

Amino acids also exist in a zwitterionic form at pH 7. The amino group is protonated (pKa ~9.4). The carboylic acid group is deprotonated (carboxylate; pKa ~2.2).

Amino acid structures differ at the side chain (R-groups). Abbreviations: three or one letter codes Amino acids (except glycine) have chiral centers: - Rotate the plane of plane-polarized light and are optically active.

Amino acid carbons are named in sequenceusing the Greek alphabet (, , , , ) starting at the carbon between the carboxyl and amino groups. CH

COO

H3N

CH2

CH2

CH2

CH2

NH3

Configuration of biological chiral compounds is defined in relation to glyceraldehyde (L- & D-) D - dextrorotatory (rotating light to the right) L - levorotatory (rotating light to the left)

BUT L or D designation for an amino acid does NOT reflect its ability to rotate plane polarized light in a particular direction!

The amino acids in proteins are L isomers.

C

COO

H3N

CH3

HC

COO

H3N

CH3

H

(S)-AlanineL-Alanine

C

H

H3C

NH3

COO

1

23

S

 

(2) Amino Acids: Structural Classification (Table 3-1, p. 78)

Cystine residues provide structural stability of proteins through intramolecular or intermolecular disulfide bonds.

Oxidation

Reduction

D-amino acids are found in a few small peptides, including some peptides of bacterial cell walls and certain antibiotics (such as penicillin).

D-GluD-Ala

(a) Acidity and Basicity of amino acids

pKa for the –COOH group in amino acids is 2 ~ 2.3, two

pH units lower than that of ordinary aliphatic carboxylic acid (pKa of CH3COOH = 4.6).

Glycine is 100 times more acidic than acetic acid. •ppKa for the –NH3

+ group in amino acids is 9 ~ 10, one

pH unit lower than that of ordinary aliphatic amine (pKa of

CH3NH3+ = 10.6).

TThe amino group of glycine is 10 times less basic than the amino groups of methylamine.

(b) Titration Curve of Amino Acids

The pH at which a molecule’s net charge is zero is called the isoelectric point or the pI  For two ionizable groups: pI = ? (such as carboxyl & amino)

pKa1 + pKa2

pI = 2

A good buffer at ~ pH 6. pI =

Histidine

(4) Functions  1. Chemical Messengers: Neurotransmitters are roughly divided into small molecules & peptidic (neuropetides), these are further classified as inhibitor and excitatory.

(A) Inhibitory Neurotransmitters Glycine (-OOC-CH2-NH3

+)

– binds a receptor that depolarizes the synapse by Cl- release – involved in motor and sensory functions -Aminobutyric acid (-OOC-(CH2)3-NH3

+) – GABA– Glutamic acid derivative– Most common neurotransmitter in brain– Huntington’s disease - altered levels (B) Excitatory Neurotransmitters Glutamic acid and Aspartic acid: learning and memory Epinephrine (=adrenaline) and norepinephrine are derived from tyrosine .

2. Monomeric subunits of proteins All proteins are composed of some or all of the 20

"standard" amino acids ‒ two new amino acids have been recently discovered!Discovery of 21st amino acid: (Selenocystein)Discovery of 22nd amino acid: (Pyrrollysine)

3. Energy metabolites – many are essential nutrients and can be used as precursors to other molecules.

[2] Peptides and Proteins (MW > 10,000): Polymers of amino acids

Energetically unfavourable (G > 0) Couple with energetically favourable reaction(s) (Leaving group activation) (Lehninger Fig 27-14, p.1052.)

Peptide synthesis:

Serylglycyltyrosylalanylleucine.

Ser-Gly-Tyr-Ala-Leu

SGTAL

N-terminus C-terminus

Peptide bonds are stable: t1/2 = 7 yrs in cells due to high G‡ of the hydrolysis reaction.

Peptides (and proteins) have their unique pI values depending on the a.a. compositions.

Biologically active peptides: oxytocin, bradykinin, vasopressin, etc. insulin, glucagon,

(3) Deduced amino acid sequences from DNA sequences

Protein function 3-D structure Sequence

The goal is to learn, from sequence, as much information as possible on its structure, function, and its evolutionary history.

[4] Protein Sequences and Evolution  Genes and proteins from closely related organisms

should be similar.

The sequences increasingly diverge as the evolutionary distance between two organisms increases.

Conserved a.a. residues: amino acid residues essential for function and structure are conserved throughout the evolution.

Variable residues: Those less important vary over time. ⇒ polymorphism

Protein family: A group of proteins with significant sequence similarity (>25%), and/or with similar structure and function.

Likely share common evolutionary origin.

Ser proteinases: chymotrypsin, trypsin, elastase, etc.

Cytochrome P450 family.

Homologs, paralogs (gene duplication), orthologs (speciation)

Multiple sequence alignment & Conservative Substitution

Homologs are identified by comparing multiple sequences of a protein from different organisms.

Multiple sequences are aligned to maximize the sequence similarity.

Conservative substitution by a chemically similar a.a. residue (Asp and Glu, Lys and Arg, Trp and Phe, etc) is given a high score during alignment according to the scoring system such as Blosum62.