From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1mr9.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1mr9.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1mr9| PDB=1mr9 | SCENE= }} | | {{STRUCTURE_1mr9| PDB=1mr9 | SCENE= }} |
| | | | |
| - | '''Crystal structure of Streptogramin A Acetyltransferase with acetyl-CoA bound'''
| + | ===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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12771141}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12771141 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_12771141}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 28: |
Line 32: |
| | [[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 01:37:39 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:17:36 2008'' |
Revision as of 17:17, 28 July 2008
Template:STRUCTURE 1mr9
Crystal structure of Streptogramin A Acetyltransferase with acetyl-CoA bound
Template:ABSTRACT PUBMED 12771141
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
Page seeded by OCA on Mon Jul 28 20:17:36 2008
