2a49
From Proteopedia
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|PDB= 2a49 |SIZE=350|CAPTION= <scene name='initialview01'>2a49</scene>, resolution 1.43Å | |PDB= 2a49 |SIZE=350|CAPTION= <scene name='initialview01'>2a49</scene>, resolution 1.43Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=TEM:N-(2-HYDROXY-4-OXO-BUTYL)-N-(3-OXO-TRANSPROPENYL)AMINE'>TEM</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= bla, shv1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 Klebsiella pneumoniae]) | |GENE= bla, shv1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 Klebsiella pneumoniae]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1rcj|1rcj]], [[2a3u|2A3U]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a49 OCA], [http://www.ebi.ac.uk/pdbsum/2a49 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a49 RCSB]</span> | ||
}} | }} | ||
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[[Category: Padayatti, P S.]] | [[Category: Padayatti, P S.]] | ||
[[Category: Totir, M A.]] | [[Category: Totir, M A.]] | ||
| - | [[Category: EPE]] | ||
| - | [[Category: MA4]] | ||
| - | [[Category: TEM]] | ||
[[Category: beta-lactam hydrolase]] | [[Category: beta-lactam hydrolase]] | ||
[[Category: beta-lactamase]] | [[Category: beta-lactamase]] | ||
| Line 40: | Line 40: | ||
[[Category: penicillinase]] | [[Category: penicillinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:47:42 2008'' |
Revision as of 22:47, 30 March 2008
| |||||||
| , resolution 1.43Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | bla, shv1 (Klebsiella pneumoniae) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 1rcj, 2A3U
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of clavulanic acid bound to E166A variant of SHV-1 beta-lactamase
Overview
Antibiotic resistance mediated by constantly evolving beta-lactamases is a serious threat to human health. The mechanism of inhibition of these enzymes by therapeutic beta-lactamase inhibitors is probed using a novel approach involving Raman microscopy and x-ray crystallography. We have presented here the high resolution crystal structures of the beta-lactamase inhibitors sulbactam and clavulanic acid bound to the deacylation-deficient E166A variant of SHV-1 beta-lactamase. Our previous Raman measurements have identified the trans-enamine species for both inhibitors and were used to guide the soaking time and concentration to achieve full occupancy of the active sites. The two inhibitor-bound x-ray structures revealed a linear trans-enamine intermediate covalently attached to the active site Ser-70 residue. This intermediate was thought to play a key role in the transient inhibition of class A beta-lactamases. Both the Raman and x-ray data indicated that the clavulanic acid intermediate is decarboxylated. When compared with our previously determined tazobactam-bound inhibitor structure, our new inhibitor-bound structures revealed an increased disorder in the tail region of the inhibitors as well as in the enamine skeleton. The x-ray crystallographic observations correlated with the broadening of the O-C=C-N (enamine) symmetric stretch Raman band near 1595 cm(-1). Band broadening in the sulbactam and clavulanic acid inter-mediates reflected a heterogeneous conformational population that results from variations of torsional angles in the O-(C=O)-C=C=NH-C skeleton. These observations led us to conclude that the conformational stability of the trans-enamine form is critical for their transient inhibitory efficacy.
About this Structure
2A49 is a Single protein structure of sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA.
Reference
High resolution crystal structures of the trans-enamine intermediates formed by sulbactam and clavulanic acid and E166A SHV-1 {beta}-lactamase., Padayatti PS, Helfand MS, Totir MA, Carey MP, Carey PR, Bonomo RA, van den Akker F, J Biol Chem. 2005 Oct 14;280(41):34900-7. Epub 2005 Jul 29. PMID:16055923
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