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1q2q
From Proteopedia
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|PDB= 1q2q |SIZE=350|CAPTION= <scene name='initialview01'>1q2q</scene>, resolution 1.40Å | |PDB= 1q2q |SIZE=350|CAPTION= <scene name='initialview01'>1q2q</scene>, resolution 1.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=WY2:(6,7-DIHYDRO-5H-CYCLOPENTA[D]IMIDAZO[2,1-B]THIAZOL-2-YL]-4,7-DIHYDRO[1,4]THIAZEPINE-3,6-DICARBOXYLIC+ACID'>WY2</scene> | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=WY2:(6,7-DIHYDRO-5H-CYCLOPENTA[D]IMIDAZO[2,1-B]THIAZOL-2-YL]-4,7-DIHYDRO[1,4]THIAZEPINE-3,6-DICARBOXYLIC+ACID'>WY2</scene> |
| - | + | |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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae]) | |GENE= BLA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 Enterobacter cloacae]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1q2p|1Q2P]], [[1shv|1SHV]], [[1ong|1ONG]], [[1onh|1ONH]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2q OCA], [http://www.ebi.ac.uk/pdbsum/1q2q PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1q2q RCSB]</span> | ||
}} | }} | ||
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[[Category: Nukaga, M.]] | [[Category: Nukaga, M.]] | ||
[[Category: Venkatesan, A M.]] | [[Category: Venkatesan, A M.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: WY2]] | ||
[[Category: beta-lactam antibiotic]] | [[Category: beta-lactam antibiotic]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
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[[Category: inhibition]] | [[Category: inhibition]] | ||
| - | ''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 23:08:00 2008'' |
Revision as of 20:08, 30 March 2008
| |||||||
| , resolution 1.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | BLA (Enterobacter cloacae) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 1Q2P, 1SHV, 1ONG, 1ONH
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Enterobacter cloacae GC1 class C beta-lactamase complexed with penem WAY185229
Overview
The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine beta-lactamase inhibitors is described. These compounds proved to be very potent inhibitors of the TEM-1 and AmpC beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. In combination with piperacillin, their in vitro activities enhanced susceptibility of all class C resistant strains from various bacteria. Crystallographic structures of a serine-bound reaction intermediate of 17 with the class A SHV-1 and class C GC1 enzymes have been established to resolutions of 2.0 and 1.4 A, respectively, and refined to R-factors equal 0.163 and 0.145. In both beta-lactamases, a seven-membered 1,4-thiazepine ring has formed. The stereogenic C7 atom in the ring has the R configuration in the SHV-1 intermediate and has both R and S configurations in the GC1 intermediate. Hydrophobic stacking interactions between the tricyclic C7 substituent and a tyrosine side chain, rather than electrostatic or hydrogen bonding by the C3 carboxylic acid group, dominate in both complexes. The formation of the 1,4- thiazepine ring structures is proposed based on a 7-endo-trig cyclization.
About this Structure
1Q2Q is a Single protein structure of sequence from Enterobacter cloacae. Full crystallographic information is available from OCA.
Reference
Structure-activity relationship of 6-methylidene penems bearing tricyclic heterocycles as broad-spectrum beta-lactamase inhibitors: crystallographic structures show unexpected binding of 1,4-thiazepine intermediates., Venkatesan AM, Gu Y, Dos Santos O, Abe T, Agarwal A, Yang Y, Petersen PJ, Weiss WJ, Mansour TS, Nukaga M, Hujer AM, Bonomo RA, Knox JR, J Med Chem. 2004 Dec 16;47(26):6556-68. PMID:15588091
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