Reaction participants Show >> << Hide
- Name help_outline (R)-lactate Identifier CHEBI:16004 (Beilstein: 4655978) help_outline Charge -1 Formula C3H5O3 InChIKeyhelp_outline JVTAAEKCZFNVCJ-UWTATZPHSA-M SMILEShelp_outline C[C@@H](O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 23 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ATP Identifier CHEBI:30616 (Beilstein: 3581767) help_outline Charge -4 Formula C10H12N5O13P3 InChIKeyhelp_outline ZKHQWZAMYRWXGA-KQYNXXCUSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,280 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline D-alanine Identifier CHEBI:57416 Charge 0 Formula C3H7NO2 InChIKeyhelp_outline QNAYBMKLOCPYGJ-UWTATZPHSA-N SMILEShelp_outline C[C@@H]([NH3+])C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 24 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP Identifier CHEBI:456216 (Beilstein: 3783669) help_outline Charge -3 Formula C10H12N5O10P2 InChIKeyhelp_outline XTWYTFMLZFPYCI-KQYNXXCUSA-K SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 841 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline D-alanyl-(R)-lactate Identifier CHEBI:61166 Charge 0 Formula C6H11NO4 InChIKeyhelp_outline QLYOONKPELZQGZ-QWWZWVQMSA-N SMILEShelp_outline C[C@@H]([NH3+])C(=O)O[C@H](C)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline phosphate Identifier CHEBI:43474 Charge -2 Formula HO4P InChIKeyhelp_outline NBIIXXVUZAFLBC-UHFFFAOYSA-L SMILEShelp_outline OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 992 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:37347 | RHEA:37348 | RHEA:37349 | RHEA:37350 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Purification and characterization of the VanB ligase associated with type B vancomycin resistance in Enterococcus faecalis V583.
Meziane-Cherif D., Badet-Denisot M.A., Evers S., Courvalin P., Badet B.
Acquired resistance to glycopeptides in enterococci is associated with the production of D-Alanine:D-Alanine ligase-related proteins. The VanA protein associated with high-level vancomycin and teicoplanin resistance (VanA phenotype) synthesizes a new peptidoglycan precursor, D-alanine-D-lactate, t ... >> More
Acquired resistance to glycopeptides in enterococci is associated with the production of D-Alanine:D-Alanine ligase-related proteins. The VanA protein associated with high-level vancomycin and teicoplanin resistance (VanA phenotype) synthesizes a new peptidoglycan precursor, D-alanine-D-lactate, that has reduced glycopeptide affinity. Production of a similar protein, VanB, is induced in strains that display variable levels of vancomycin resistance but remain susceptible to teicoplanin (VanB phenotype). This paper describes the over-production, purification and characterization of VanB. Comparison of kinetic parameters of the two Van enzymes suggests that differences in catalytic efficiency could account, at least in part, for the various levels of vancomycin resistance. << Less
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Role of Arg301 in substrate orientation and catalysis in subsite 2 of D-alanine:D-alanine (D-lactate) ligase from Leuconostoc mesenteroides: a molecular docking study.
Neuhaus F.C.
D-alanine:D-alanine (D-lactate) ligase (ADP) from Leuconostoc mesenteroides synthesizes the depsipeptide, D-alanyl-D-lactate, in addition to D-alanyl-D-alanine, when D-alanine and D-lactate are incubated simultaneously. The depsipeptide is responsible for the intrinsic resistance of this organism ... >> More
D-alanine:D-alanine (D-lactate) ligase (ADP) from Leuconostoc mesenteroides synthesizes the depsipeptide, D-alanyl-D-lactate, in addition to D-alanyl-D-alanine, when D-alanine and D-lactate are incubated simultaneously. The depsipeptide is responsible for the intrinsic resistance of this organism to vancomycin. The orientations of D-lactate and D-alanine in subsite 2 of the ligase that result in both nucleophile generation and subsequent attack on the electrophilic center of D-alanyl phosphate in subsite 1 are not known. A molecular docking study using AutoDock 4 suggests a role for Arg301 in determining these orientations of acceptor substrate in subsite 2 for both nucleophile generation and subsequent attack on the phosphate intermediate. With D-lactate a bifurcated H-bond from Arg301 to the R-OH of D-lactate may account for its orientation and nucleophile activation. This orientation is observed when the guanidino side chain of this residue is flexible. D-alanine adopts an orientation that utilizes H-bonding to water 2882 and the D-alanyl phosphate in subsite 1. Both of these orientations provide mechanisms of deprotonation and place the nucleophile within 3.2A of the electrophilic carbonyl of the D-alanyl phosphate intermediate for formation of the transition state. These results suggest that Arg301 has a dual function in a sequential reaction mechanism, i.e. substrate orientation in subsite 2 as well as stabilization of the transition state. In addition, these docking studies provide insights for inhibitor design targeted to this subsite of the ligase. << Less
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VanD-type glycopeptide-resistant Enterococcus faecium BM4339.
Perichon B., Reynolds P., Courvalin P.
Enterococcus faecium BM4339 was constitutively resistant to vancomycin (MIC, 64 microg/ml) and to low levels of teicoplanin (MIC, 4 microg/ml). A 605-bp product obtained with the V1 and V2 primers for amplification of genes encoding D-Ala:D-Ala ligases and related glycopeptide resistance proteins ... >> More
Enterococcus faecium BM4339 was constitutively resistant to vancomycin (MIC, 64 microg/ml) and to low levels of teicoplanin (MIC, 4 microg/ml). A 605-bp product obtained with the V1 and V2 primers for amplification of genes encoding D-Ala:D-Ala ligases and related glycopeptide resistance proteins was sequenced after cloning. The deduced amino acid sequence had 69% identity with VanA and VanB and 43% identity with VanC, consistent with the finding that BM4339 synthesized peptidoglycan precursors terminating in D-lactate. This new type of glycopeptide resistance phenotype was designated VanD. << Less
Antimicrob Agents Chemother 41:2016-2018(1997) [PubMed] [EuropePMC]