View source for 4oak


==Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine-D-Alanine and copper (II)==
<StructureSection load='4oak' size='340' side='right'caption='[[4oak]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4oak]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_gallinarum Enterococcus gallinarum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OAK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PE3:3,6,9,12,15,18,21,24,27,30,33,36,39-TRIDECAOXAHENTETRACONTANE-1,41-DIOL'>PE3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4oak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oak OCA], [https://pdbe.org/4oak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oak RCSB], [https://www.ebi.ac.uk/pdbsum/4oak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oak ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9JN36_ENTGA Q9JN36_ENTGA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Vancomycin resistance in Gram-positive bacteria is due to production of cell-wall precursors ending in d-Ala-d-Lac or d-Ala-d-Ser, to which vancomycin exhibits low binding affinities, and to the elimination of the high-affinity precursors ending in d-Ala-d-Ala. Depletion of the susceptible high-affinity precursors is catalyzed by the zinc-dependent d,d-peptidases VanX and VanY acting on dipeptide (d-Ala-d-Ala) or pentapeptide (UDP-MurNac-l-Ala-d-Glu-l-Lys-d-Ala-d-Ala), respectively. Some of the vancomycin resistance operons encode VanXY d,d-carboxypeptidase, which hydrolyzes both di- and pentapeptide. The molecular basis for the diverse specificity of Van d,d-peptidases remains unknown. We present the crystal structures of VanXYC and VanXYG in apo and transition state analog-bound forms and of VanXYC in complex with the d-Ala-d-Ala substrate and d-Ala product. Structural and biochemical analysis identified the molecular determinants of VanXY dual specificity. VanXY residues 110-115 form a mobile cap over the catalytic site, whose flexibility is involved in the switch between di- and pentapeptide hydrolysis. Structure-based alignment of the Van d,d-peptidases showed that VanY enzymes lack this element, which promotes binding of the penta- rather than that of the dipeptide. The structures also highlight the molecular basis for selection of d-Ala-ending precursors over the modified resistance targets. These results illustrate the remarkable adaptability of the d,d-peptidase fold in response to antibiotic pressure via evolution of specific structural elements that confer hydrolytic activity against vancomycin-susceptible peptidoglycan precursors.

Structural basis for the evolution of vancomycin resistance D,D-peptidases.,Meziane-Cherif D, Stogios PJ, Evdokimova E, Savchenko A, Courvalin P Proc Natl Acad Sci U S A. 2014 Apr 7. PMID:24711382<ref>PMID:24711382</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4oak" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus gallinarum]]
[[Category: Large Structures]]
[[Category: Anderson WF]]
[[Category: Courvalin P]]
[[Category: Di Leo R]]
[[Category: Evdokimova E]]
[[Category: Meziane-Cherif D]]
[[Category: Savchenko A]]
[[Category: Stogios PJ]]
[[Category: Yim V]]