1kvl: Difference between revisions

Revision as of 23:13, 2 May 2008

X-ray Crystal Structure of AmpC S64G Mutant beta-Lactamase in Complex with Substrate and Product Forms of Cephalothin

OverviewOverview

Beta-lactamases hydrolyze beta-lactam antibiotics and are the leading cause of bacterial resistance to these drugs. Although beta-lactamases have been extensively studied, structures of the substrate-enzyme and product-enzyme complexes have proven elusive. Here, the structure of a mutant AmpC in complex with the beta-lactam cephalothin in its substrate and product forms was determined by X-ray crystallography to 1.53 A resolution. The acyl-enzyme intermediate between AmpC and cephalothin was determined to 2.06 A resolution. The ligand undergoes a dramatic conformational change as the reaction progresses, with the characteristic six-membered dihydrothiazine ring of cephalothin rotating by 109 degrees. These structures correspond to all three intermediates along the reaction path and provide insight into substrate recognition, catalysis, and product expulsion.

About this StructureAbout this Structure

1KVL is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Structural milestones in the reaction pathway of an amide hydrolase: substrate, acyl, and product complexes of cephalothin with AmpC beta-lactamase., Beadle BM, Trehan I, Focia PJ, Shoichet BK, Structure. 2002 Mar;10(3):413-24. PMID:12005439 Page seeded by OCA on Fri May 2 23:13:15 2008

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

OCA

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 [[Image:1kvl.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1kvl |SIZE=350|CAPTION= <scene name='initialview01'>1kvl</scene>, resolution 1.53&Aring;
+The line below this paragraph, containing "STRUCTURE_1kvl", 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=CLS:CEPHALOTHIN'>CLS</scene>, <scene name='pdbligand=KCP:2-[CARBOXY-(2-THIOPHEN-2-YL-ACETYLAMINO)-METHYL]-5-METHYL-3,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC+ACID'>KCP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=THN:2-[CARBOXY-(2-THIOPHEN-2-YL-ACETYLAMINO)-METHYL]-5-METHYLENE-5,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC+ACID'>THN</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/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= K12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
+-->
-|DOMAIN=
+{{STRUCTURE_1kvl|  PDB=1kvl  |  SCENE=  }}
-|RELATEDENTRY=[[1kvm|1KVM]], [[1ke4|1KE4]], [[2bls|2BLS]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvl OCA], [http://www.ebi.ac.uk/pdbsum/1kvl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kvl RCSB]</span>
-}}
 '''X-ray Crystal Structure of AmpC S64G Mutant beta-Lactamase in Complex with Substrate and Product Forms of Cephalothin'''
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 [[Category: Shoichet, B K.]]
 [[Category: Trehan, I.]]
-[[Category: amide hydrolase]]
+[[Category: Amide hydrolase]]
-[[Category: beta-lactamase]]
+[[Category: Beta-lactamase]]
-[[Category: cephalothin]]
+[[Category: Cephalothin]]
-[[Category: product-enzyme complex]]
+[[Category: Product-enzyme complex]]
-[[Category: substrate-enzyme complex]]
+[[Category: Substrate-enzyme complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 23:13:15 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:54:09 2008''