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| ==Crystal Structure of Vancomycin Resistance D,D-dipeptidase VanXYg== | | ==Crystal Structure of Vancomycin Resistance D,D-dipeptidase VanXYg== |
- | <StructureSection load='4f78' size='340' side='right' caption='[[4f78]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4f78' size='340' side='right'caption='[[4f78]], [[Resolution|resolution]] 1.95Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4f78]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F78 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F78 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f78]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F78 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4f78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f78 OCA], [https://pdbe.org/4f78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f78 RCSB], [https://www.ebi.ac.uk/pdbsum/4f78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f78 ProSAT]</span></td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4muq|4muq]], [[4mur|4mur]], [[4mus|4mus]], [[4mut|4mut]], [[4oak|4oak]]</td></tr>
| + | |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vanXYG, vanYG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</td></tr>
| + | |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f78 OCA], [http://pdbe.org/4f78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f78 RCSB], [http://www.ebi.ac.uk/pdbsum/4f78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f78 ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/Q9KHL8_ENTFL Q9KHL8_ENTFL] |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]] | + | [[Category: Enterococcus faecalis]] |
- | [[Category: Anderson, W F]] | + | [[Category: Large Structures]] |
- | [[Category: Structural genomic]] | + | [[Category: Anderson WF]] |
- | [[Category: Courvalin, P]] | + | [[Category: Courvalin P]] |
- | [[Category: Egorova, O]] | + | [[Category: Di Leo R]] |
- | [[Category: Evdokimova, E]] | + | [[Category: Egorova O]] |
- | [[Category: Kudritska, M]] | + | [[Category: Evdokimova E]] |
- | [[Category: Leo, R Di]] | + | [[Category: Kudritska M]] |
- | [[Category: Meziane-Cherif, D]] | + | [[Category: Meziane-Cherif D]] |
- | [[Category: Minasov, G]] | + | [[Category: Minasov G]] |
- | [[Category: Savchenko, A]] | + | [[Category: Savchenko A]] |
- | [[Category: Stogios, P J]] | + | [[Category: Stogios PJ]] |
- | [[Category: Wawrzak, Z]] | + | [[Category: Wawrzak Z]] |
- | [[Category: Yim, V]] | + | [[Category: Yim V]] |
- | [[Category: Alpha+beta protein]]
| + | |
- | [[Category: Csgid]]
| + | |
- | [[Category: D-alanine-d-alanine]]
| + | |
- | [[Category: D-dipeptidase]]
| + | |
- | [[Category: Hedgehog/dd-peptidase fold]]
| + | |
- | [[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]]
| + | |
| Structural highlights
4f78 is a 1 chain structure with sequence from Enterococcus faecalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Ligands: | , , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q9KHL8_ENTFL
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meziane-Cherif D, Stogios PJ, Evdokimova E, Savchenko A, Courvalin P. Structural basis for the evolution of vancomycin resistance D,D-peptidases. Proc Natl Acad Sci U S A. 2014 Apr 7. PMID:24711382 doi:http://dx.doi.org/10.1073/pnas.1402259111
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