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4x6t
From Proteopedia
(Difference between revisions)
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<StructureSection load='4x6t' size='340' side='right' caption='[[4x6t]], [[Resolution|resolution]] 1.40Å' scene=''> | <StructureSection load='4x6t' size='340' side='right' caption='[[4x6t]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4x6t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x6t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X6T FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Y6:3-[(2R)-2-(DIHYDROXYBORANYL)-2-{[(2R)-2-{[(4-ETHYL-2,3-DIOXO-3,4-DIHYDROPYRAZIN-1(2H)-YL)CARBONYL]AMINO}-2-(4-HYDROXYPHENYL)ACETYL]AMINO}ETHYL]BENZOIC+ACID'>3Y6</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Y6:3-[(2R)-2-(DIHYDROXYBORANYL)-2-{[(2R)-2-{[(4-ETHYL-2,3-DIOXO-3,4-DIHYDROPYRAZIN-1(2H)-YL)CARBONYL]AMINO}-2-(4-HYDROXYPHENYL)ACETYL]AMINO}ETHYL]BENZOIC+ACID'>3Y6</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaC, blaA, Rv2068c, MTCY49.07c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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='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=4x6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6t OCA], [http://pdbe.org/4x6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6t RCSB], [http://www.ebi.ac.uk/pdbsum/4x6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6t ProSAT]</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=4x6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x6t OCA], [http://pdbe.org/4x6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x6t RCSB], [http://www.ebi.ac.uk/pdbsum/4x6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x6t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BlaC, the single chromosomally encoded beta-lactamase of Mycobacterium tuberculosis, has been identified as a promising target for novel therapies that rely upon beta-lactamase inhibition. Boronic acid transition-state inhibitors (BATSIs) are a class of beta-lactamase inhibitors which permit rational inhibitor design by combinations of various R1 and R2 side chains. To explore the structural determinants of effective inhibition, we screened a panel of 25 BATSIs to explore key structure-function relationships. We identified a cefoperazone analogue, EC19, which displayed slow, time-dependent inhibition against BlaC with a potency similar to that of clavulanate (Ki* of 0.65 +/- 0.05 muM). To further characterize the molecular basis of inhibition, we solved the crystallographic structure of the EC19-BlaC(N172A) complex and expanded our analysis to variant enzymes. The results of this structure-function analysis encourage the design of a novel class of beta-lactamase inhibitors, BATSIs, to be used against Mycobacterium tuberculosis. | ||
| + | |||
| + | Inhibiting the beta-Lactamase of Mycobacterium tuberculosis (Mtb) with Novel Boronic Acid Transition-State Inhibitors (BATSIs).,Kurz SG, Hazra S, Bethel CR, Romagnoli C, Caselli E, Prati F, Blanchard JS, Bonomo RA ACS Infect Dis. 2015 Jun 12;1(6):234-42. doi: 10.1021/acsinfecdis.5b00003. Epub, 2015 Apr 15. PMID:27622739<ref>PMID:27622739</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4x6t" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase|Beta-lactamase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
| + | [[Category: Myctu]] | ||
[[Category: Hazra, S]] | [[Category: Hazra, S]] | ||
[[Category: Beta-lactam]] | [[Category: Beta-lactam]] | ||
Revision as of 06:13, 18 April 2018
M.tuberculosis betalactamase complexed with inhibitor EC19
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