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1ehi

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[[Image:1ehi.jpg|left|200px]]<br /><applet load="1ehi" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ehi, resolution 2.38&Aring;" />
 
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'''D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES'''<br />
 
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==Overview==
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==D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES==
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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.
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<StructureSection load='1ehi' size='340' side='right'caption='[[1ehi]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<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>
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1EHI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Leuconostoc_mesenteroides Leuconostoc mesenteroides] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=PHY:'>PHY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EHI OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
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<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>
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==Reference==
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<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>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=10801495 10801495]
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</table>
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[[Category: D-alanine--D-alanine ligase]]
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== Function ==
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[https://www.uniprot.org/uniprot/DDL_LEUMM DDL_LEUMM] Cell wall formation.[HAMAP-Rule:MF_00047]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eh/1ehi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Leuconostoc mesenteroides]]
[[Category: Leuconostoc mesenteroides]]
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[[Category: Single protein]]
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[[Category: Healy VL]]
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[[Category: Healy, V L.]]
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[[Category: Jorczak-Baillass J]]
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[[Category: Jorczak-Baillass, J.]]
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[[Category: Knox JR]]
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[[Category: Knox, J R.]]
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[[Category: Kuzin AP]]
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[[Category: Kuzin, A P.]]
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[[Category: Sun T]]
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[[Category: Sun, T.]]
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[[Category: Walsh CT]]
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[[Category: Walsh, C T.]]
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[[Category: ADP]]
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[[Category: MG]]
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[[Category: PHY]]
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[[Category: atp-binding. grasp motif for atp.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:27:50 2008''
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Current revision

D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES

PDB ID 1ehi

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