2fq6: Difference between revisions

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==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.

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==

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[[Category: Escherichia coli]]

[[Category: Single protein]]

[[Category: Junop, M.S.]]

[[Category: Junop, M S.]]

[[Category: P3F]]

[[Category: plp cofactor covalently bound to p3f inhibitor]]

[[Category: protein-inhibitor complex]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 14: / Line 14: @@
 [[Category: Escherichia coli]]
 [[Category: Single protein]]
-[[Category: Junop, M.S.]]
+[[Category: Junop, M S.]]
 [[Category: P3F]]
 [[Category: plp cofactor covalently bound to p3f inhibitor]]
 [[Category: protein-inhibitor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:23:53 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:24:01 2008''