View source for 3isg


==Structure of the class D beta-lactamase OXA-1 in complex with doripenem==
<StructureSection load='3isg' size='340' side='right'caption='[[3isg]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3isg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ISG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ISG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></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=3isg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3isg OCA], [https://pdbe.org/3isg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3isg RCSB], [https://www.ebi.ac.uk/pdbsum/3isg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3isg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLO1_ECOLX BLO1_ECOLX] This is an oxacillin-hydrolyzing beta-lactamase.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/is/3isg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3isg ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
The clinical efficacy of carbapenem antibiotics depends on their resistance to the hydrolytic action of beta-lactamase enzymes. The structure of the class D beta-lactamase OXA-1 as an acyl complex with the carbapenem doripenem was determined to 1.4 A resolution. Unlike most class A and class C carbapenem complexes, the acyl carbonyl oxygen in the OXA-1-doripenem complex is bound in the oxyanion hole. Interestingly, no water molecules were observed in the vicinity of the acyl linkage, providing an explanation for why carbapenems inhibit OXA-1. The side chain amine of K70 remains fully carboxylated in the acyl structure, and the resulting carbamate group forms a hydrogen bond to the alcohol of the 6alpha-hydroxyethyl moiety of doripenem. The carboxylate attached to the beta-lactam ring of doripenem is stabilized by a salt bridge to K212 and a hydrogen bond with T213, in lieu of the interaction with an arginine side chain found in most other beta-lactamase-beta-lactam complexes (e.g., R244 in the class A member TEM-1). This novel set of interactions with the carboxylate results in a major shift of the carbapenem's pyrroline ring compared to the structure of the same ring in meropenem bound to OXA-13. Additionally, bond angles of the pyrroline ring suggest that after acylation, doripenem adopts the Delta(1) tautomer. These findings provide important insights into the role that carbapenems may have in the inactivation process of class D beta-lactamases.

The 1.4 A Crystal Structure of the Class D beta-Lactamase OXA-1 Complexed with Doripenem.,Schneider KD, Karpen ME, Bonomo RA, Leonard DA, Powers RA Biochemistry. 2009 Nov 24. PMID:19919101<ref>PMID:19919101</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3isg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Powers RA]]