4mut: Difference between revisions

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-{{STRUCTURE_4mut|  PDB=4mut  |  SCENE=  }}
-===Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine===
-{{ABSTRACT_PUBMED_24711382}}
-==About this Structure==
+==Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine==
-[[4mut]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_49573 Atcc 49573]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MUT OCA].
+<StructureSection load='4mut' size='340' side='right'caption='[[4mut]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4mut]] 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=4MUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUT 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]] 2.25&#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=DAL:D-ALANINE'>DAL</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>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4mut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mut OCA], [https://pdbe.org/4mut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mut RCSB], [https://www.ebi.ac.uk/pdbsum/4mut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mut 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.
-==Reference==
+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>
-<ref group="xtra">PMID:024711382</ref><references group="xtra"/><references/>
-[[Category: Atcc 49573]]
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Anderson, W F.]]
+</div>
-[[Category: CSGID, Center for Structural Genomics of Infectious Diseases.]]
+<div class="pdbe-citations 4mut" style="background-color:#fffaf0;"></div>
-[[Category: Courvalin, P.]]
+== References ==
-[[Category: Evdokimova, E.]]
+<references/>
-[[Category: Leo, R Di.]]
+__TOC__
-[[Category: Meziane-Cherif, D.]]
+</StructureSection>
-[[Category: Savchenko, A.]]
+[[Category: Enterococcus gallinarum]]
-[[Category: Stogios, P J.]]
+[[Category: Large Structures]]
-[[Category: Yim, V.]]
+[[Category: Anderson WF]]
-[[Category: Alpha+beta protein]]
+[[Category: Courvalin P]]
-[[Category: Antibiotic resistance]]
+[[Category: Di Leo R]]
-[[Category: Center for structural genomics of infectious disease]]
+[[Category: Evdokimova E]]
-[[Category: Csgid]]
+[[Category: Meziane-Cherif D]]
-[[Category: D-dipeptidase]]
+[[Category: Savchenko A]]
-[[Category: D-pentapeptidase]]
+[[Category: Stogios PJ]]
-[[Category: Hedgehog/dd-peptidase fold]]
+[[Category: Yim V]]
-[[Category: Hydrolase]]
-[[Category: Merops m15b subfamily]]
-[[Category: Metallopeptidase]]
-[[Category: National institute of allergy and infectious disease]]
-[[Category: Niaid]]
-[[Category: Vancomycin resistance]]
-[[Category: Zn2+-dependent d]]