Unlike mammals, bacteria encode enzymes that synthesize branched-chain amino
acids. The pyridoxal 50-phosphate-dependent transaminase performs the final
biosynthetic step in these pathways, converting keto acid precursors into -amino
acids. The branched-chain amino-acid transaminase from Mycobacterium
tuberculosis (MtIlvE) has been crystallized and its structure has been solved at
1.9 angstrom resolution. The MtIlvE monomer is composed of two domains that
interact to form the active site. The biologically active form of IlvE is a
homodimer in which each monomer contributes a substrate-specificity loop to the
partner molecule. Additional substrate selectivity may be imparted by a
conserved N-terminal Phe30 residue, which has previously been observed to shield
the active site in the type IV fold homodimer. The active site of MtIlvE
contains density corresponding to bound PMP, which is likely to be a consequence
of the presence of tryptone in the crystallization medium. Additionally, two
cysteine residues are positioned at the dimer interface for disulfide-bond
formation under oxidative conditions. It is unknown whether they are involved in
any regulatory activities analogous to those of the human mitochondrial
branched-chain amino-acid transaminase.
