1iem
From Proteopedia
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|PDB= 1iem |SIZE=350|CAPTION= <scene name='initialview01'>1iem</scene>, resolution 2.30Å | |PDB= 1iem |SIZE=350|CAPTION= <scene name='initialview01'>1iem</scene>, resolution 2.30Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=CB4:PINACOL[[2-AMINO-ALPHA-(1-CARBOXY-1-METHYLETHOXYIMINO)-4-THIAZOLEACETYL]AMINO]METHANEBORONATE'>CB4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1fsy|1FSY]], [[1fsw|1FSW]], [[2bls|2BLS]], [[3bls|3BLS]], [[1ga9|1GA9]], [[1c3b|1C3B]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1iem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iem OCA], [http://www.ebi.ac.uk/pdbsum/1iem PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1iem RCSB]</span> | ||
}} | }} | ||
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[[Category: Prati, F.]] | [[Category: Prati, F.]] | ||
[[Category: Shoichet, B K.]] | [[Category: Shoichet, B K.]] | ||
| - | [[Category: CB4]] | ||
| - | [[Category: PO4]] | ||
[[Category: beta-lactamase]] | [[Category: beta-lactamase]] | ||
[[Category: cephalosporinase]] | [[Category: cephalosporinase]] | ||
[[Category: serine hydrolase]] | [[Category: serine hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:18:44 2008'' |
Revision as of 18:18, 30 March 2008
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 1FSY, 1FSW, 2BLS, 3BLS, 1GA9, 1C3B
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of AmpC beta-lactamase from E. coli in Complex with a Boronic Acid Inhibitor (1, CefB4)
Overview
Third-generation cephalosporins are widely used beta-lactam antibiotics that resist hydrolysis by beta-lactamases. Recently, mutant beta-lactamases that rapidly inactivate these drugs have emerged. To investigate why third-generation cephalosporins are relatively stable to wild-type class C beta-lactamases and how mutant enzymes might overcome this, the structures of the class C beta-lactamase AmpC in complex with the third-generation cephalosporin ceftazidime and with a transition-state analogue of ceftazidime were determined by X-ray crystallography to 2.0 and 2.3 A resolution, respectively. Comparison of the acyl-enzyme structures of ceftazidime and loracarbef, a beta-lactam substrate, reveals that the conformation of ceftazidime in the active site differs from that of substrates. Comparison of the structures of the acyl-enzyme intermediate and the transition-state analogue suggests that ceftazidime blocks formation of the tetrahedral transition state, explaining why it is an inhibitor of AmpC. Ceftazidime cannot adopt a conformation competent for catalysis due to steric clashes that would occur with conserved residues Val211 and Tyr221. The X-ray crystal structure of the mutant beta-lactamase GC1, which has improved activity against third-generation cephalosporins, suggests that a tandem tripeptide insertion in the Omega loop, which contains Val211, has caused a shift of this residue and also of Tyr221 that would allow ceftazidime and other third-generation cephalosporins to adopt a more catalytically competent conformation. These structural differences may explain the extended spectrum activity of GC1 against this class of cephalosporins. In addition, the complexed structure of the transition-state analogue inhibitor (K(i) 20 nM) with AmpC reveals potential opportunities for further inhibitor design.
About this Structure
1IEM is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: implications for resistance mutations and inhibitor design., Powers RA, Caselli E, Focia PJ, Prati F, Shoichet BK, Biochemistry. 2001 Aug 7;40(31):9207-14. PMID:11478888
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