1epv
From Proteopedia
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ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM D-CYCLOSERINE
Overview
Alanine racemase (EC 5.1.1.1) catalyzes the interconversion of alanine, enantiomers, and thus represents the first committed step involved in, bacterial cell wall biosynthesis. Cycloserine acts as a suicide inhibitor, of alanine racemase and as such, serves as an antimicrobial agent. The, chemical means by which cycloserine inhibits alanine racemase is unknown., Through spectroscopic assays, we show here evidence of a pyridoxal, derivative (arising from either isomer of cycloserine) saturated at the, C4' carbon position. We additionally report the L- and D-cycloserine, inactivated crystal structures of Bacillus stearothermophilus alanine, racemase, which corroborates the spectroscopy via evidence of a, 3-hydroxyisoxazole pyridoxamine derivative. Upon the basis of the kinetic, and structural properties of both the L- and D-isomers of the inhibitor, we propose a mechanism of alanine racemase inactivation by cycloserine., This pathway involves an initial transamination step followed by, tautomerization to form a stable aromatic adduct, a scheme similar to that, seen in cycloserine inactivation of aminotransferases.
About this Structure
1EPV is a Single protein structure of sequence from Geobacillus stearothermophilus with DCS as ligand. Active as Alanine racemase, with EC number 5.1.1.1 Full crystallographic information is available from OCA.
Reference
A side reaction of alanine racemase: transamination of cycloserine., Fenn TD, Stamper GF, Morollo AA, Ringe D, Biochemistry. 2003 May 20;42(19):5775-83. PMID:12741835
Page seeded by OCA on Tue Nov 20 14:12:56 2007
