1vft
From Proteopedia
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Crystal structure of L-cycloserine-bound form of alanine racemase from D-cycloserine-producing Streptomyces lavendulae
Overview
Alanine racemase (ALR), an enzyme that catalyzes the interconversion of, Ala enantiomers, is essential for the synthesis of the bacterial cell, wall. We have shown that it is harder to inhibit the catalytic activity of, ALR from D-cycloserine (DCS)-producing Streptomyces lavendulae than that, from Escherichia coli by DCS. To obtain structural evidence for the fact, that Streptomyces ALR displays resistance to DCS, we determined the, precise nature of the x-ray crystal structures of the cycloserine-free and, cycloserine enantiomer-bound forms of Streptomyces ALR at high, resolutions. Streptomyces ALR takes a dimer structure, which is formed by, interactions between the N-terminal domain of one monomer with the, C-terminal domain of its partner. Each of the two active sites of ALR, which is generated as a result of the formation of the dimer structure, is, composed of pyridoxal 5'-phosphate (PLP), the PLP-binding residue Lys(38), and the amino acids in the immediate environment of the pyridoxal, cofactor. The current model suggests that each active site of Streptomyces, ALR maintains a larger space and takes a more rigid conformation than that, of Bacillus stearothermophilus ALR determined previously. Furthermore, we, show that Streptomyces ALR results in a slow conversion to a final form of, a pyridoxal derivative arising from either isomer of cycloserine, which, inhibits the catalytic activity noncompetitively. In fact, the slow, conversion is confirmed by the fact that each enzyme bound cycloserine, derivative, which is bound to PLP, takes an asymmetric structure.
About this Structure
1VFT is a Protein complex structure of sequences from Streptomyces lavendulae with CL and DCS as ligands. Active as Alanine racemase, with EC number 5.1.1.1 Full crystallographic information is available from OCA.
Reference
Structural evidence that alanine racemase from a D-cycloserine-producing microorganism exhibits resistance to its own product., Noda M, Matoba Y, Kumagai T, Sugiyama M, J Biol Chem. 2004 Oct 29;279(44):46153-61. Epub 2004 Aug 9. PMID:15302886
Page seeded by OCA on Sat Nov 24 22:22:11 2007
