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| | <StructureSection load='1ehi' size='340' side='right'caption='[[1ehi]], [[Resolution|resolution]] 2.38Å' scene=''> | | <StructureSection load='1ehi' size='340' side='right'caption='[[1ehi]], [[Resolution|resolution]] 2.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ehi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"ascococcus_mesenteroides"_tsenkovskii_1878 "ascococcus mesenteroides" tsenkovskii 1878]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EHI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EHI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ehi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"ascococcus_mesenteroides"_tsenkovskii_1878 "ascococcus mesenteroides" tsenkovskii 1878]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EHI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EHI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PHY:1(S)-AMINOETHYL-(2-CARBOXYPROPYL)PHOSPHORYL-PHOSPHINIC+ACID'>PHY</scene></td></tr> | + | </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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PHY:1(S)-AMINOETHYL-(2-CARBOXYPROPYL)PHOSPHORYL-PHOSPHINIC+ACID'>PHY</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2dln|2dln]], [[1iov|1iov]], [[1iow|1iow]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2dln|2dln]], [[1iov|1iov]], [[1iow|1iow]]</div></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/D-alanine--D-alanine_ligase D-alanine--D-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.4 6.3.2.4] </span></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--D-alanine_ligase D-alanine--D-alanine ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.4 6.3.2.4] </span></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=1ehi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ehi OCA], [http://pdbe.org/1ehi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ehi RCSB], [http://www.ebi.ac.uk/pdbsum/1ehi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ehi 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=1ehi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ehi OCA], [https://pdbe.org/1ehi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ehi RCSB], [https://www.ebi.ac.uk/pdbsum/1ehi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ehi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/P71454_LEUME P71454_LEUME]] Cell wall formation (By similarity).[SAAS:SAAS005905_004_000867][HAMAP-Rule:MF_00047] | + | [[https://www.uniprot.org/uniprot/P71454_LEUME P71454_LEUME]] Cell wall formation (By similarity).[SAAS:SAAS005905_004_000867][HAMAP-Rule:MF_00047] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Structural highlights
Function
[P71454_LEUME] Cell wall formation (By similarity).[SAAS:SAAS005905_004_000867][HAMAP-Rule:MF_00047]
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
BACKGROUND: The bacterial cell wall and the enzymes that synthesize it are targets of glycopeptide antibiotics (vancomycins and teicoplanins) and beta-lactams (penicillins and cephalosporins). Biosynthesis of cell wall peptidoglycan requires a crosslinking of peptidyl moieties on adjacent glycan strands. The D-alanine-D-alanine transpeptidase, which catalyzes this crosslinking, is the target of beta-lactam antibiotics. Glycopeptides, in contrast, do not inhibit an enzyme, but bind directly to D-alanine-D-alanine and prevent subsequent crosslinking by the transpeptidase. Clinical resistance to vancomycin in enterococcal pathogens has been traced to altered ligases producing D-alanine-D-lactate rather than D-alanine-D-alanine. RESULTS: The structure of a D-alanine-D-lactate ligase has been determined by multiple anomalous dispersion (MAD) phasing to 2.4 A resolution. Co-crystallization of the Leuconostoc mesenteroides LmDdl2 ligase with ATP and a di-D-methylphosphinate produced ADP and a phosphinophosphate analog of the reaction intermediate of cell wall peptidoglycan biosynthesis. Comparison of this D-alanine-D-lactate ligase with the known structure of DdlB D-alanine-D-alanine ligase, a wild-type enzyme that does not provide vancomycin resistance, reveals alterations in the size and hydrophobicity of the site for D-lactate binding (subsite 2). A decrease was noted in the ability of the ligase to hydrogen bond a substrate molecule entering subsite 2. CONCLUSIONS: Structural differences at subsite 2 of the D-alanine-D-lactate ligase help explain a substrate specificity shift (D-alanine to D-lactate) leading to remodeled cell wall peptidoglycan and vancomycin resistance in Gram-positive pathogens.
Enzymes of vancomycin resistance: the structure of D-alanine-D-lactate ligase of naturally resistant Leuconostoc mesenteroides.,Kuzin AP, Sun T, Jorczak-Baillass J, Healy VL, Walsh CT, Knox JR Structure. 2000 May 15;8(5):463-70. PMID:10801495[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kuzin AP, Sun T, Jorczak-Baillass J, Healy VL, Walsh CT, Knox JR. Enzymes of vancomycin resistance: the structure of D-alanine-D-lactate ligase of naturally resistant Leuconostoc mesenteroides. Structure. 2000 May 15;8(5):463-70. PMID:10801495
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