2gqn
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Cystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-Benzamide
OverviewOverview
The biosynthesis of methionine is an attractive antibiotic target given, its importance in protein and DNA metabolism and its absence in mammals., We have performed a high-throughput screen of the methionine biosynthesis, enzyme cystathionine beta-lyase (CBL) against a library of 50 000 small, molecules and have identified several compounds that inhibit CBL enzyme, activity in vitro. These hit molecules were of two classes: those that, blocked CBL activity with mixed steady-state inhibition and those that, covalently interacted with the enzyme at the active site pyridoxal, phosphate cofactor with slow-binding inhibition kinetics. We determined, the crystal structure of one of the slow-binding inhibitors in complex, with CBL and used this structure as a guide in the synthesis of a small, focused library of analogues, some of which had improved enzyme inhibition, properties. These studies provide the first lead molecules for, antimicrobial agents that target cystathionine beta-lyase in methionine, biosynthesis.
About this StructureAbout this Structure
2GQN is a Single protein structure of sequence from Escherichia coli with BLP as ligand. Active as Cystathionine beta-lyase, with EC number 4.4.1.8 Full crystallographic information is available from OCA.
ReferenceReference
Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function., Ejim LJ, Blanchard JE, Koteva KP, Sumerfield R, Elowe NH, Chechetto JD, Brown ED, Junop MS, Wright GD, J Med Chem. 2007 Feb 22;50(4):755-64. PMID:17300162
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