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| | <StructureSection load='1q2q' size='340' side='right'caption='[[1q2q]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='1q2q' size='340' side='right'caption='[[1q2q]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1q2q]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"aerobacter_cloacae"_(jordan_1890)_bergey_et_al._1923 "aerobacter cloacae" (jordan 1890) bergey et al. 1923]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q2Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Q2Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1q2q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q2Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q2p|1q2p]], [[1shv|1shv]], [[1ong|1ong]], [[1onh|1onh]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BLA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 "Aerobacter cloacae" (Jordan 1890) Bergey et al. 1923])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2q OCA], [https://pdbe.org/1q2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q2q RCSB], [https://www.ebi.ac.uk/pdbsum/1q2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q2q ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/1q2q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q2q RCSB], [http://www.ebi.ac.uk/pdbsum/1q2q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q2q ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q59401_ENTCL Q59401_ENTCL] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q2/1q2q_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q2/1q2q_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Enterobacter cloacae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bonomo, R A]] | + | [[Category: Bonomo RA]] |
| - | [[Category: Hujer, A]] | + | [[Category: Hujer A]] |
| - | [[Category: Knox, J R]] | + | [[Category: Knox JR]] |
| - | [[Category: Mansour, T S]] | + | [[Category: Mansour TS]] |
| - | [[Category: Nukaga, M]] | + | [[Category: Nukaga M]] |
| - | [[Category: Venkatesan, A M]] | + | [[Category: Venkatesan AM]] |
| - | [[Category: Beta-lactam antibiotic]]
| + | |
| - | [[Category: Drug design]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibition]]
| + | |
| Structural highlights
Function
Q59401_ENTCL
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. 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. J Med Chem. 2004 Dec 16;47(26):6556-68. PMID:15588091 doi:10.1021/jm049680x
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