Transcript
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.
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