1mr7

<table><tr><td colspan='2'>[[1mr7]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_19434 Atcc 19434]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MR7 FirstGlance]. <br>

</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mr9|1mr9]], [[1mrl|1mrl]]</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=1mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mr7 OCA], [http://pdbe.org/1mr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mr7 RCSB], [http://www.ebi.ac.uk/pdbsum/1mr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1mr7 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/VATD_ENTFC VATD_ENTFC]] Inactivates the A compounds of streptogramin antibiotics by acetylation, thus providing resistance to these antibiotics.

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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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== References ==

<references/>

[[Category: Atcc 19434]]

[[Category: Courvalin, P]]

[[Category: Kehoe, L E]]

[[Category: Murray, I A]]

[[Category: Rafferty, J B]]

[[Category: Snidwongse, J]]

[[Category: Transferase]]