1mr9
From Proteopedia
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|PDB= 1mr9 |SIZE=350|CAPTION= <scene name='initialview01'>1mr9</scene>, resolution 3.00Å | |PDB= 1mr9 |SIZE=350|CAPTION= <scene name='initialview01'>1mr9</scene>, resolution 3.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ACO:ACETYL COENZYME *A'>ACO</scene> | + | |LIGAND= <scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1mr7|1MR7]], [[1mrl|1MRL]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mr9 OCA], [http://www.ebi.ac.uk/pdbsum/1mr9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mr9 RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Rafferty, J B.]] | [[Category: Rafferty, J B.]] | ||
[[Category: Snidwongse, J.]] | [[Category: Snidwongse, J.]] | ||
| - | [[Category: ACO]] | ||
[[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 | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:20:02 2008'' |
Revision as of 19:20, 30 March 2008
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| , resolution 3.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Related: | 1MR7, 1MRL
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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