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Information on EC 6.3.2.4 - D-Alanine-D-alanine ligase and Organism(s) Leuconostoc mesenteroides and UniProt Accession P71454

for references in articles please use BRENDA:EC6.3.2.4
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EC Tree
IUBMB Comments
Involved with EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate---L-alanine ligase), EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine---D-glutamate ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide---D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram).
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Leuconostoc mesenteroides
UNIPROT: P71454
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The taxonomic range for the selected organisms is: Leuconostoc mesenteroides
The enzyme appears in selected viruses and cellular organisms
Synonyms
d-alanine:d-alanine ligase, d-alanine-d-alanine ligase, d-ala-d-ala ligase, d-ala:d-ala ligase, vanb ligase, abddl, ttddl, tmddl, ecddlb, d-alanyl-d-alanine synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D-Ala-D-Ala ligase
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D-Ala-D-Ala synthetase
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D-alanine:D-alanine (D-lactate) ligase (ADP)
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D-Alanine:D-alanine ligase
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D-Alanyl-D-alanine synthetase
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D-Alanylalanine synthetase
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Synthetase, D-alanylalanine
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VanA
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VanB ligase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxylic acid amide formation
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carboxamide formation
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PATHWAY SOURCE
PATHWAYS
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-, -, -
SYSTEMATIC NAME
IUBMB Comments
D-alanine:D-alanine ligase (ADP-forming)
Involved with EC 6.3.2.7 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---L-lysine ligase) or EC 6.3.2.13 (UDP-N-acetylmuramoyl-L-alanyl-D-glutamate---2,6-diaminopimelate ligase), EC 6.3.2.8 (UDP-N-acetylmuramate---L-alanine ligase), EC 6.3.2.9 (UDP-N-acetylmuramoyl-L-alanine---D-glutamate ligase) and EC 6.3.2.10 (UDP-N-acetylmuramoyl-tripeptide---D-alanyl-D-alanine ligase) in the synthesis of a cell-wall peptide (click here for diagram).
CAS REGISTRY NUMBER
COMMENTARY hide
9023-63-6
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + D-Ala + D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
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-
?
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
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?
ATP + 2 D-Ala
ADP + phosphate + D-Ala-D-Ala
show the reaction diagram
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?
ATP + 2 D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
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?
ATP + D-Ala + D-lactate
ADP + phosphate + D-Ala-D-lactate
show the reaction diagram
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depsipeptide D-Ala-D-lactate is responsible for the intrinsic resistance of Leuconostoc mesenteroides to vancomycin
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 2 D-alanine
ADP + phosphate + D-alanyl-D-alanine
show the reaction diagram
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
resistant to vancomycin
Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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Phe261 is a key specificity determinant in the alpha-helical cap of the Omega-loop when folded into the closed conformation, molecular docking, overview. The hydroxyl of Tyr261 plays an instrumental role in determining non-productive docking orientations of dlactate, i.e. D-lactate-OH as an H-bond donor to the Tyr261-OH or D-lactate as an H-bond donor to the phosphoryl of the intermediate D-alanyl phosphate, and the D-lactate-COO- as an H-bond acceptor for the Tyr261-OH. Arg301 is required for the activation of the nucleophilic D-lactate for D-Ala-D-lactate formation. Ligand binding docking structure study, involving also the transition-state analogue, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
P71454_LEUME
377
0
41826
TrEMBL
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular docking study on the orientations of substrates. Residue 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. 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-Ala adopts an orientation that utilizes H-bonding to water 2882 and the D-Ala phosphate in subsite 1. Both of these orientations provide mechanisms of deprotonation and place the nucleophile within 3.2 A of the electrophilic carbonyl of the D-Ala phosphate intermediate for formation of the transition state
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F261Y
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mutation of the Omega loop, inactive mutant
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overproduction in Escherichia coli, the vancomycin resistant enzyme has Phe261 instead of Tyr. The Tyr to Phe substitution on the active site omega-loop in the D-Ala-D-Ala ligases is a molecular indicator of both the ability to make D-Ala-D-Lac and intrinsic resistance to the vancomycin class of glycopeptide antibiotics
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Park, I.S.; Walsh, C.T.
D-Alanyl-D-lactate and D-alanyl-D-alanine synthesis by D-alanyl-D-alanine ligase from vancomycin-resistant Leuconostoc mesenteroides. Effects of a phenylalanine 261 to tyrosine mutation
J. Biol. Chem.
272
9210-9214
1997
Leuconostoc mesenteroides (P71454), Leuconostoc mesenteroides
Manually annotated by BRENDA team
Neuhaus, F.C.
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
J. Mol. Graph. Model.
28
728-734
2010
Leuconostoc mesenteroides
Manually annotated by BRENDA team
Neuhaus, F.C.
Role of the omega loop in specificity determination in subsite 2 of the D-alanine:D-alanine (D-lactate) ligase from Leuconostoc mesenteroides: a molecular docking study
J. Mol. Graph. Model.
30
31-37
2011
Leuconostoc mesenteroides
Manually annotated by BRENDA team