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| [[Image:1ehi.jpg|left|200px]]
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| {{Structure
| | ==D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES== |
| |PDB= 1ehi |SIZE=350|CAPTION= <scene name='initialview01'>1ehi</scene>, resolution 2.38Å
| | <StructureSection load='1ehi' size='340' side='right'caption='[[1ehi]], [[Resolution|resolution]] 2.38Å' scene=''> |
| |SITE= | | == Structural highlights == |
| |LIGAND= <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>
| | <table><tr><td colspan='2'>[[1ehi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Leuconostoc_mesenteroides Leuconostoc mesenteroides]. 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> |
| |ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38Å</td></tr> |
| |GENE=
| | <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> |
| |DOMAIN=
| | <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> |
| |RELATEDENTRY=[[2dln|2DLN]], [[1iov|1IOV]], [[1iow|1IOW]]
| | </table> |
| |RESOURCES=<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://www.ebi.ac.uk/pdbsum/1ehi PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ehi RCSB]</span>
| | == Function == |
| }}
| | [https://www.uniprot.org/uniprot/DDL_LEUMM DDL_LEUMM] Cell wall formation.[HAMAP-Rule:MF_00047] |
| | | == Evolutionary Conservation == |
| '''D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES'''
| | [[Image:Consurf_key_small.gif|200px|right]] |
| | | Check<jmol> |
| | | <jmolCheckbox> |
| ==Overview== | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eh/1ehi_consurf.spt"</scriptWhenChecked> |
| 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.
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | | <text>to colour the structure by Evolutionary Conservation</text> |
| ==About this Structure== | | </jmolCheckbox> |
| 1EHI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Leuconostoc_mesenteroides Leuconostoc mesenteroides]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EHI OCA].
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ehi ConSurf]. |
| | | <div style="clear:both"></div> |
| ==Reference==
| | __TOC__ |
| 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:[http://www.ncbi.nlm.nih.gov/pubmed/10801495 10801495]
| | </StructureSection> |
| [[Category: D-alanine--D-alanine ligase]] | | [[Category: Large Structures]] |
| [[Category: Leuconostoc mesenteroides]] | | [[Category: Leuconostoc mesenteroides]] |
| [[Category: Single protein]]
| | [[Category: Healy VL]] |
| [[Category: Healy, V L.]] | | [[Category: Jorczak-Baillass J]] |
| [[Category: Jorczak-Baillass, J.]] | | [[Category: Knox JR]] |
| [[Category: Knox, J R.]] | | [[Category: Kuzin AP]] |
| [[Category: Kuzin, A P.]] | | [[Category: Sun T]] |
| [[Category: Sun, T.]] | | [[Category: Walsh CT]] |
| [[Category: Walsh, C T.]] | |
| [[Category: atp-binding. grasp motif for atp.]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:02:46 2008''
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