4mut: Difference between revisions
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==Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine== | ==Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine== | ||
<StructureSection load='4mut' size='340' side='right' caption='[[4mut]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='4mut' size='340' side='right'caption='[[4mut]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mut]] is a 2 chain structure with sequence from [ | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9JN36_ENTGA Q9JN36_ENTGA] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 22: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Enterococcus gallinarum]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Anderson WF]] | ||
[[Category: Courvalin | [[Category: Courvalin P]] | ||
[[Category: | [[Category: Di Leo R]] | ||
[[Category: | [[Category: Evdokimova E]] | ||
[[Category: Meziane-Cherif | [[Category: Meziane-Cherif D]] | ||
[[Category: Savchenko | [[Category: Savchenko A]] | ||
[[Category: Stogios | [[Category: Stogios PJ]] | ||
[[Category: Yim | [[Category: Yim V]] | ||
Revision as of 13:11, 28 December 2022
Crystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-AlanineCrystal structure of vancomycin resistance D,D-dipeptidase/D,D-pentapeptidase VanXYc D59S mutant in complex with D-Alanine
Structural highlights
FunctionPublication Abstract from PubMedVancomycin 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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