1q2p
From Proteopedia
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| - | [[Image:1q2p.gif|left|200px]] | + | [[Image:1q2p.gif|left|200px]] |
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| - | '''SHV-1 class A beta-lactamase complexed with penem WAY185229''' | + | {{Structure |
| + | |PDB= 1q2p |SIZE=350|CAPTION= <scene name='initialview01'>1q2p</scene>, resolution 2.00Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene> and <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= [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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 Klebsiella pneumoniae]) | ||
| + | }} | ||
| + | |||
| + | '''SHV-1 class A beta-lactamase complexed with penem WAY185229''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Q2P is a [ | + | 1Q2P 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=1Q2P OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15588091 15588091] |
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Klebsiella pneumoniae]] | [[Category: Klebsiella pneumoniae]] | ||
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[[Category: MA4]] | [[Category: MA4]] | ||
[[Category: WY2]] | [[Category: WY2]] | ||
| - | [[Category: beta-lactam | + | [[Category: beta-lactam antibiotic]] |
[[Category: drug design]] | [[Category: drug design]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: inhibition]] | [[Category: inhibition]] | ||
| - | ''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 13:32:11 2008'' |
Revision as of 11:32, 20 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | BLA (Klebsiella pneumoniae) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SHV-1 class A 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
1Q2P is a Single protein structure of sequence from Klebsiella pneumoniae. 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
Page seeded by OCA on Thu Mar 20 13:32:11 2008
