View source for 1mrl


==Crystal structure of streptogramin A acetyltransferase with dalfopristin==
<StructureSection load='1mrl' size='340' side='right'caption='[[1mrl]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mrl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MRL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MRL 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOL:5-(2-DIETHYLAMINO-ETHANESULFONYL)-21-HYDROXY-10-ISOPROPYL-11,19-DIMETHYL-9,26-DIOXA-3,15,28-TRIAZA-TRICYCLO[23.2.1.00,255]OCTACOSA-1(27),12,17,19,25(28)-PENTAENE-2,8,14,23-TETRAONE'>DOL</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=1mrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mrl OCA], [https://pdbe.org/1mrl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mrl RCSB], [https://www.ebi.ac.uk/pdbsum/1mrl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mrl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VATD_ENTFC VATD_ENTFC] Inactivates the A compounds of streptogramin antibiotics by acetylation, thus providing resistance to these antibiotics.
== 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/mr/1mrl_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=1mrl ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Synercid, a new semisynthetic streptogramin-derived antibiotic containing dalfopristin and quinupristin, is used in treatment of life-threatening infections caused by glycopeptide-resistant Enterococcus faecium and other bacterial pathogens. However, dissemination of genes encoding virginiamycin acetyltransferases, enzymes that confer resistance to streptogramins, threatens to limit the medical utility of the quinupristin-dalfopristin combination. Here we present structures of virginiamycin acetyltransferase D (VatD) determined at 1.8 A resolution in the absence of ligands, at 2.8 A resolution bound to dalfopristin, and at 3.0 A resolution in the presence of acetyl-coenzyme A. Dalfopristin is bound by VatD in a similar conformation to that described previously for the streptogramin virginiamycin M1. However, specific interactions with the substrate are altered as a consequence of a conformational change in the pyrollidine ring that is propagated to adjacent constituents of the dalfopristin macrocycle. Inactivation of dalfopristin involves acetyl transfer from acetyl-coenzyme A to the sole (O-18) hydroxy group of the antibiotic that lies close to the side chain of the strictly conserved residue, His-82. Replacement of residue 82 by alanine is accompanied by a fall in specific activity of &gt;105-fold, indicating that the imidazole moiety of His-82 is a major determinant of catalytic rate enhancement by VatD. The structure of the VatD-dalfopristin complex can be used to predict positions where further structural modification of the drug might preclude enzyme binding and thereby circumvent Synercid resistance.

Structural basis of Synercid (quinupristin-dalfopristin) resistance in Gram-positive bacterial pathogens.,Kehoe LE, Snidwongse J, Courvalin P, Rafferty JB, Murray IA J Biol Chem. 2003 Aug 8;278(32):29963-70. Epub 2003 May 27. PMID:12771141<ref>PMID:12771141</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 1mrl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus faecium]]
[[Category: Large Structures]]
[[Category: Courvalin P]]
[[Category: Kehoe LE]]
[[Category: Murray IA]]
[[Category: Rafferty JB]]
[[Category: Snidwongse J]]