1mr9
From Proteopedia
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| - | [[Image:1mr9.gif|left|200px]] | + | [[Image:1mr9.gif|left|200px]] |
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| - | '''Crystal structure of Streptogramin A Acetyltransferase with acetyl-CoA bound''' | + | {{Structure |
| + | |PDB= 1mr9 |SIZE=350|CAPTION= <scene name='initialview01'>1mr9</scene>, resolution 3.00Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ACO:ACETYL COENZYME *A'>ACO</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of Streptogramin A Acetyltransferase with acetyl-CoA bound''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1MR9 is a [ | + | 1MR9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MR9 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12771141 12771141] |
[[Category: Enterococcus faecium]] | [[Category: Enterococcus faecium]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[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 Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:47:18 2008'' |
Revision as of 10:47, 20 March 2008
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| , resolution 3.00Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Streptogramin A Acetyltransferase with acetyl-CoA bound
Overview
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 >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.
About this Structure
1MR9 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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