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
m (Protected "1mrl" [edit=sysop:move=sysop])
Line 1: Line 1:
-
[[Image:1mrl.png|left|200px]]
+
==Crystal structure of streptogramin A acetyltransferase with dalfopristin==
 +
<StructureSection load='1mrl' size='340' side='right' caption='[[1mrl]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1mrl]] is a 3 chain structure with 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=1MRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MRL FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOL:5-(2-DIETHYLAMINO-ETHANESULFONYL)-21-HYDROXY-10-ISOPROPYL-11,19-DIMETHYL-9,26-DIOXA-3,15,28-TRIAZA-TRICYCLO[23.2.1.00,255]OCTACOSA-1(27),12,17,19,25(28)-PENTAENE-2,8,14,23-TETRAONE'>DOL</scene><br>
 +
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mr7|1mr7]], [[1mr9|1mr9]]</td></tr>
 +
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mrl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1mrl RCSB], [http://www.ebi.ac.uk/pdbsum/1mrl PDBsum]</span></td></tr>
 +
<table>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mr/1mrl_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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.
-
{{STRUCTURE_1mrl| PDB=1mrl | SCENE= }}
+
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<ref>PMID:12771141</ref>
-
===Crystal structure of streptogramin A acetyltransferase with dalfopristin===
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
{{ABSTRACT_PUBMED_12771141}}
+
== References ==
-
 
+
<references/>
-
==About this Structure==
+
__TOC__
-
[[1mrl]] is a 3 chain structure with 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=1MRL OCA].
+
</StructureSection>
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:012771141</ref><references group="xtra"/>
+
[[Category: Enterococcus faecium]]
[[Category: Enterococcus faecium]]
[[Category: Courvalin, P.]]
[[Category: Courvalin, P.]]

Revision as of 14:32, 28 September 2014

Crystal structure of streptogramin A acetyltransferase with dalfopristin

1mrl, resolution 2.80Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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