1epv
From Proteopedia
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'''ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM D-CYCLOSERINE''' | '''ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM D-CYCLOSERINE''' | ||
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[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
[[Category: Stamper, G F.]] | [[Category: Stamper, G F.]] | ||
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Revision as of 12:23, 2 May 2008
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. 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 Fri May 2 15:23:08 2008