2a3u
From Proteopedia
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| - | [[Image:2a3u.gif|left|200px]] | + | [[Image:2a3u.gif|left|200px]] |
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| - | '''Crystal structure of sulbactam bound to E166A variant of SHV-1 beta-lactamase''' | + | {{Structure |
| + | |PDB= 2a3u |SIZE=350|CAPTION= <scene name='initialview01'>2a3u</scene>, resolution 1.34Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=TSL:TRANS-ENAMINE+INTERMEDIATE+OF+SULBACTAM'>TSL</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene> and <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID'>EPE</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] | ||
| + | |GENE= bla, shv1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 Klebsiella pneumoniae]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of sulbactam bound to E166A variant of SHV-1 beta-lactamase''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2A3U is a [ | + | 2A3U is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A3U OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16055923 16055923] |
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Klebsiella pneumoniae]] | [[Category: Klebsiella pneumoniae]] | ||
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[[Category: penicillinase]] | [[Category: penicillinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:45:02 2008'' |
Revision as of 13:45, 20 March 2008
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| , resolution 1.34Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | bla, shv1 (Klebsiella pneumoniae) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of sulbactam 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
2A3U 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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