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New page: left|200px<br /><applet load="1ehi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ehi, resolution 2.38Å" /> '''D-ALANINE:D-LACTATE ...
 
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[[Image:1ehi.jpg|left|200px]]<br /><applet load="1ehi" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1ehi, resolution 2.38&Aring;" />
'''D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES'''<br />


==Overview==
==D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES==
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.
<StructureSection load='1ehi' size='340' side='right'caption='[[1ehi]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<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>
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 MG, ADP and PHY 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EHI OCA].  
</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>
 
<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>
==Reference==
<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>
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]
</table>
[[Category: D-alanine--D-alanine ligase]]
== Function ==
[https://www.uniprot.org/uniprot/DDL_LEUMM DDL_LEUMM] Cell wall formation.[HAMAP-Rule:MF_00047]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eh/1ehi_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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>
__TOC__
</StructureSection>
[[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: ADP]]
[[Category: MG]]
[[Category: PHY]]
[[Category: atp-binding. grasp motif for atp.]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:16:34 2007''

Latest revision as of 07:03, 7 February 2024

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

1ehi, resolution 2.38Å

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