Structure and Function:
A. What are the structural aspects of amino acids?
B. How do the structures of amino acids affect protein structure?
C. How do the chemical properties of the amino acid side chains contribute to the functions of proteins?
Amino Acid Stereochemistry:
A. Only L-amino acids are found in proteins
B. Chiral compounds are identified by the fact that they rotate the plane of polarized light
C. Three types of notation are used to describe chiral compounds:
a. (+) & (-) refer to the direction of rotation of polarized light.
b. R and S refer to the absolute (vs. relational) stereochemical relationship of the four substituents at a chiral carbon. (Used by O. Chemists)
c. D and L refer to the biochemical (chemical) relationship between glyceraldehyde (the simplest sugar with an asymmetric center) and other compounds derived from it.
1. Chemists use R and S; they have no relationship to optical rotation
2. Biochemists use D and L, which specify a stereochemical relationship between the compound of interest and the parent sugar (glyceraldehyde). This system is used for historical reasons. Again, D and L do not relate to optical rotation.
Optically active amino acids are racemized (converted to D-L mixtures) when a chiral carbon passes through a symmetrical intermediate (boiling in strong base). This is why proteins are hydrolyzed in acidic medium
1. Aliphatic side chain amino acids: Gly, Ala, Val, Leu, Ile
Provide differing degrees of bulk for packing amino acids into protein structures. Gly can be found in areas of protein structure that require tight packing.
Cysteine can form disulfide bonds between distant portions of the polypeptide chain to stabilize intra- inter-chain structures. (A + 2 RSH --> RS-SR + AH2) Serine and threonine provide points of attachment for sugars and act as components of the active sites of some enzymes.
Tyr can be involved in catalysis as the phenolate anion. All three contribute to the UV absorption in proteins. Tyr and Trp also react with Folin reagent in the Lowry protein determination.
All side chains have 4 carbons, hence their bulks are nearly equal. (Lys pKa = 10.5, Arg pKa = 12.5, His = 6.0) These residues are active in many catalytic events as well as forming ionic bonds that aid in positioning acidic substrates. As bases, they can participate in nucleophilic reactions. The imidazole group of histidine is capable of co-ordinating metal ions.
5. Acidic amino acids: Asp, Glu, Asn, Gln (amides involved in N-linked CHO's)
Asp (pKa = 3.9), Glu (pKa =4.25) are encountered in active sites where bond polarization is required. Also act to position basic groups. Provide anionic sites on the surfaces of proteins.
a. gamma amino glutamic acid (GABA), a neurotransmitter, is formed via decarboxylation of glutamic acid
b. thyroxine: tyrosine modified with iodine, made in the thyroid gland and regulates metabolic rate
c. gamma-carboxyglutamate (requires vitamin K) involved in binding Ca2+ in blood clotting
