1hkv

From Proteopedia

Revision as of 14:20, 18 December 2007

MYCOBACTERIUM DIAMINOPIMELATE DICARBOXYLASE (LYSA)

Overview

The Mycobacterium tuberculosis lysA gene encodes the enzyme, meso-diaminopimelate decarboxylase (DAPDC), a pyridoxal-5'-phosphate, (PLP)-dependent enzyme. The enzyme catalyzes the final step in the lysine, biosynthetic pathway converting meso-diaminopimelic acid (DAP) to, l-lysine. The lysA gene of M. tuberculosis H37Rv has been established as, essential for bacterial survival in immunocompromised mice, demonstrating, that de novo biosynthesis of lysine is essential for in vivo viability., Drugs targeted against DAPDC could be efficient anti-tuberculosis drugs, and the three-dimensional structure of DAPDC from M. tuberculosis, complexed with reaction product lysine and the ternary complex with PLP, and lysine in the active site has been determined. The first structure of, a DAPDC confirms its classification as a fold type III PLP-dependent, enzyme. The structure shows a stable 2-fold dimer in head-to-tail, arrangement of a triose-phosphate isomerase (TIM) barrel-like alpha/beta, domain and a C-terminal beta sheet domain, similar to the ornithine, decarboxylase (ODC) fold family. PLP is covalently bound via an internal, aldimine, and residues from both domains and both subunits contribute to, the binding pocket. Comparison of the structure with eukaryotic ODCs, in, particular with a di-fluoromethyl ornithine (DMFO)-bound ODC from, Trypanosoma bruceii, indicates that corresponding DAP-analogues might be, potential inhibitors for mycobacterial DAPDCs.

About this Structure

1HKV is a Single protein structure of sequence from Mycobacterium tuberculosis with LYS and PLP as ligands. Active as Diaminopimelate decarboxylase, with EC number 4.1.1.20 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis., Gokulan K, Rupp B, Pavelka MS Jr, Jacobs WR Jr, Sacchettini JC, J Biol Chem. 2003 May 16;278(20):18588-96. Epub 2003 Mar 10. PMID:12637582

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