3pag: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[ | ==Crystal structure of the V130D mutant of OXA-24/40 in complex with doripenem== | ||
<StructureSection load='3pag' size='340' side='right' caption='[[3pag]], [[Resolution|resolution]] 2.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pag]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PAG FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DRW:(2S,3R,4S)-2-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-3-METHYL-4-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>DRW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3isg|3isg]], [[3pae|3pae]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaOXA-33, bla-OXA-40, blaOXA-24, blaOXA-40, oxa-24, oxa40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=470 Acinetobacter baumannii])</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=3pag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pag OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pag RCSB], [http://www.ebi.ac.uk/pdbsum/3pag PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The emergence of class D beta-lactamases with carbapenemase activity presents an enormous challenge to health practitioners, particularly with regard to the treatment of infections caused by Gram-negative pathogens such as Acinetobacter baumanii. Unfortunately, class D beta-lactamases with carbapenemase activity are resistant to beta-lactamase inhibitors. To better understand the details of the how these enzymes bind and hydrolyze carbapenems, we have determined the structures of two deacylation-deficient variants (K84D and V130D) of the class D carbapenemase OXA-24 with doripenem bound as a covalent acyl-enzyme intermediate. Doripenem adopts essentially the same configuration in both OXA-24 variant structures, but varies significantly when compared to the non-carbapenemase class D member OXA-1/doripenem complex. The alcohol of the 6alpha hydroxyethyl moiety is directed away from the general base carboxy-K84, with implications for activation of the deacylating water. The tunnel formed by the Y112/M223 bridge in the apo form of OXA-24 is largely unchanged by the binding of doripenem. The presence of this bridge, however, causes the distal pyrrolidine/sulfonamide group to bind in a drastically different conformation compared to doripenem bound to OXA-1. The resulting difference in the position of the side-chain bridge sulfur of doripenem is consistent with the hypothesis that the tautomeric state of the pyrroline ring contributes to the different carbapenem hydrolysis rates of OXA-1 and OXA-24. These findings represent a snapshot of a key step in the catalytic mechanism of an important class D enzyme, and might be useful for the design of novel inhibitors. | |||
Structures of the Class D Carbapenemase OXA-24 from Acinetobacter baumannii in Complex with Doripenem.,Schneider KD, Ortega CJ, Renck NA, Bonomo RA, Powers RA, Leonard DA J Mol Biol. 2011 Jan 6. PMID:21215758<ref>PMID:21215758</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase|Beta-lactamase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Acinetobacter baumannii]] | [[Category: Acinetobacter baumannii]] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Leonard, D A | [[Category: Leonard, D A]] | ||
[[Category: Powers, R A | [[Category: Powers, R A]] | ||
[[Category: Schneider, K D | [[Category: Schneider, K D]] | ||
[[Category: Carbapenemase]] | [[Category: Carbapenemase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Hydrolase-antibiotic complex]] | [[Category: Hydrolase-antibiotic complex]] | ||