|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1e4e' size='340' side='right'caption='[[1e4e]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='1e4e' size='340' side='right'caption='[[1e4e]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1e4e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_19434 Atcc 19434]. The December 2015 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Vancomycin'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2015_12 10.2210/rcsb_pdb/mom_2015_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E4E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1e4e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. The December 2015 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Vancomycin'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2015_12 10.2210/rcsb_pdb/mom_2015_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E4E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PHY:1(S)-AMINOETHYL-(2-CARBOXYPROPYL)PHOSPHORYL-PHOSPHINIC+ACID'>PHY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1iow|1iow]], [[1iov|1iov]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PHY:1(S)-AMINOETHYL-(2-CARBOXYPROPYL)PHOSPHORYL-PHOSPHINIC+ACID'>PHY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VANA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1352 ATCC 19434])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/D-alanine--(R)-lactate_ligase D-alanine--(R)-lactate ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.2.1 6.1.2.1] </span></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=1e4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e4e OCA], [https://pdbe.org/1e4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e4e RCSB], [https://www.ebi.ac.uk/pdbsum/1e4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e4e ProSAT]</span></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=1e4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e4e OCA], [https://pdbe.org/1e4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e4e RCSB], [https://www.ebi.ac.uk/pdbsum/1e4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e4e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VANA_ENTFC VANA_ENTFC]] Required for high-level resistance to glycopeptide antibiotics. D-Ala--D-Ala ligase of altered specificity which catalyzes ester bond formation between D-Ala and various D-hydroxy acids; produces a peptidoglycan which does not terminate in D-alanine but in D-lactate, thus preventing vancomycin or teicoplanin binding.<ref>PMID:1931965</ref>
| + | [https://www.uniprot.org/uniprot/VANA_ENTFC VANA_ENTFC] Required for high-level resistance to glycopeptide antibiotics. D-Ala--D-Ala ligase of altered specificity which catalyzes ester bond formation between D-Ala and various D-hydroxy acids; produces a peptidoglycan which does not terminate in D-alanine but in D-lactate, thus preventing vancomycin or teicoplanin binding.<ref>PMID:1931965</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 35: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 19434]] | + | [[Category: Enterococcus faecium]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| | [[Category: Vancomycin]] | | [[Category: Vancomycin]] |
| - | [[Category: Roper, D I]] | + | [[Category: Roper DI]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Cell wall]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Peptidoglycan synthesis]]
| + | |
| Structural highlights
1e4e is a 2 chain structure with sequence from Enterococcus faecium. The December 2015 RCSB PDB Molecule of the Month feature on Vancomycin by David Goodsell is 10.2210/rcsb_pdb/mom_2015_12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
VANA_ENTFC Required for high-level resistance to glycopeptide antibiotics. D-Ala--D-Ala ligase of altered specificity which catalyzes ester bond formation between D-Ala and various D-hydroxy acids; produces a peptidoglycan which does not terminate in D-alanine but in D-lactate, thus preventing vancomycin or teicoplanin binding.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
d-alanine-d-lactate ligase from Enterococcus faecium BM4147 is directly responsible for the biosynthesis of alternate cell-wall precursors in bacteria, which are resistant to the glycopeptide antibiotic vancomycin. The crystal structure has been determined with data extending to 2.5-A resolution. This structure shows that the active site has unexpected interactions and is distinct from previous models for d-alanyl-d-lactate ligase mechanistic studies. It appears that the preference of the enzyme for lactate as a ligand over d-alanine could be mediated by electrostatic effects and/or a hydrogen-bonding network, which principally involve His-244. The structure of d-alanyl-d-lactate ligase provides a revised interpretation of the molecular events that lead to vancomycin resistance.
The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA).,Roper DI, Huyton T, Vagin A, Dodson G Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8921-5. PMID:10908650[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bugg TD, Wright GD, Dutka-Malen S, Arthur M, Courvalin P, Walsh CT. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry. 1991 Oct 29;30(43):10408-15. PMID:1931965
- ↑ Roper DI, Huyton T, Vagin A, Dodson G. The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA). Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8921-5. PMID:10908650 doi:http://dx.doi.org/10.1073/pnas.150116497
|
