1mr7: Difference between revisions

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[[Image:1mr7.gif|left|200px]]
{{Seed}}
[[Image:1mr7.png|left|200px]]


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{{STRUCTURE_1mr7|  PDB=1mr7  |  SCENE=  }}  
{{STRUCTURE_1mr7|  PDB=1mr7  |  SCENE=  }}  


'''Crystal Structure of Streptogramin A Acetyltransferase'''
===Crystal Structure of Streptogramin A Acetyltransferase===




==Overview==
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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.
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{{ABSTRACT_PUBMED_12771141}}


==About this Structure==
==About this Structure==
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[[Category: Snidwongse, J.]]
[[Category: Snidwongse, J.]]
[[Category: Left-handed parallel beta-helix domain]]
[[Category: Left-handed parallel beta-helix domain]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 01:37:29 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:24:49 2008''

Revision as of 09:24, 29 July 2008

File:1mr7.png

Template:STRUCTURE 1mr7

Crystal Structure of Streptogramin A Acetyltransferase

Template:ABSTRACT PUBMED 12771141

About this Structure

1MR7 is a Single protein structure of sequence from Enterococcus faecium. Full crystallographic information is available from OCA.

Reference

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

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