This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1mrl

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1mrl.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1mrl.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1mrl| PDB=1mrl | SCENE= }}
{{STRUCTURE_1mrl| PDB=1mrl | SCENE= }}
-
'''Crystal structure of streptogramin A acetyltransferase with dalfopristin'''
+
===Crystal structure of streptogramin A acetyltransferase with dalfopristin===
-
==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 &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.
+
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 01:38:15 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:20:20 2008''

Revision as of 11:20, 27 July 2008

Image:1mrl.png

Template:STRUCTURE 1mrl

Crystal structure of streptogramin A acetyltransferase with dalfopristin

Template:ABSTRACT PUBMED 12771141

About this Structure

1MRL 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 Sun Jul 27 14:20:20 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mrl"
Personal tools