2gqn
Cystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-BenzamideCystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-Benzamide
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||||