2gqn
From Proteopedia
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'''Cystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-Benzamide''' | '''Cystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-Benzamide''' | ||
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[[Category: Junop, M S.]] | [[Category: Junop, M S.]] | ||
[[Category: Summerfield, R.]] | [[Category: Summerfield, R.]] | ||
| - | [[Category: | + | [[Category: Plp cofactor covalently bount to blp inhibitor]] |
| - | [[Category: | + | [[Category: Protein-inhibitor complex]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:24:41 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:24, 4 May 2008
Cystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-Benzamide
Overview
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 Structure
2GQN is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sun May 4 05:24:41 2008
