2gqn: Difference between revisions

Revision as of 05:24, 4 May 2008

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. 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 Page seeded by OCA on Sun May 4 05:24:41 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2gqn.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2gqn |SIZE=350|CAPTION= <scene name='initialview01'>2gqn</scene>, resolution 1.80&Aring;
+The line below this paragraph, containing "STRUCTURE_2gqn", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BLP:(5-HYDROXY-6-METHYL-4-((2-(2-(2-NITROBENZAMIDO)ACETYL)HYDRAZINYL)METHYL)PYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>BLP</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cystathionine_beta-lyase Cystathionine beta-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.8 4.4.1.8] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= metC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
+-->
-|DOMAIN=
+{{STRUCTURE_2gqn|  PDB=2gqn  |  SCENE=  }}
-|RELATEDENTRY=[[2fq6|2FQ6]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gqn OCA], [http://www.ebi.ac.uk/pdbsum/2gqn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gqn RCSB]</span>
-}}
 '''Cystathionine Beta-Lyase (CBL) from Escherichia Coli in complex with N-Hydrazinocarbonylmethyl-2-Nitro-Benzamide'''
@@ Line 28: / Line 25: @@
 [[Category: Junop, M S.]]
 [[Category: Summerfield, R.]]
-[[Category: plp cofactor covalently bount to blp inhibitor]]
+[[Category: Plp cofactor covalently bount to blp inhibitor]]
-[[Category: protein-inhibitor complex]]
+[[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 Mon Mar 31 03:20:16 2008''