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Rule : D-alanine--D-lactate ligase (VANA)

Rule Description

ID NRULE_0265
Rule name VANA
Created 2014-06-19
Protein name
Protein name
Full
D-alanine--D-lactate ligase
Short
D-Ala--D-Lac ligase
EC
EC 6.1.2.1
Gene name Not assigned
Rule Trigger BLASTP; P25051; hit=1; score=1000; pid=55ANDHAMAP; MF_00047; hit=1
Cross Reference
Gene Ontology
GO
GO:0005737, C:cytoplasm, IEA:UniProtKB-HAMAP
GO:0005886, C:plasma membrane, IEA:UniProtKB-SubCell
GO:0005524, F:ATP binding, IEA:UniProtKB-HAMAP
GO:0008716, F:D-alanine-D-alanine ligase activity, IDA:CACAO
GO:0000287, F:magnesium ion binding, IEA:UniProtKB-HAMAP
GO:0030145, F:manganese ion binding, IEA:UniProtKB-HAMAP
GO:0009252, P:peptidoglycan biosynthetic process, IEA:UniProtKB-HAMAP
GO:0008360, P:regulation of cell shape, IEA:UniProtKB-KW
GO:0046677, P:response to antibiotic, IEA:UniProtKB-KW
Enzyme and pathway databases
BioCyc
MetaCyc:MONOMER-15466, -
Family and domain databases
HAMAP
MF_00047, Dala_Dala_lig, 1
InterPro
IPR011761, ATP-grasp
IPR013815, ATP_grasp_subdomain_1
IPR013816, ATP_grasp_subdomain_2
IPR000291, D-Ala_lig_Van_CS
IPR005905, D_ala_D_ala
IPR011095, Dala_Dala_lig_C
IPR011127, Dala_Dala_lig_N
IPR016185, PreATP-grasp_dom
Pfam
PF07478, Dala_Dala_lig_C, 1
PF01820, Dala_Dala_lig_N, 1
TIGRFAMs
TIGR01205, D_ala_D_alaTIGR, 1
PROSITE
PS50975, ATP_GRASP, 1
PS00843, DALA_DALA_LIGASE_1, 1
PS00844, DALA_DALA_LIGASE_2, 1
Feature
P25051 Enterococcus faecium (Streptococcus faecium).
NP_BIND169 - 171ATP.
NP_BIND177 - 178ATP.
NP_BIND207 - 214ATP.
NP_BIND304 - 305ATP.
METAL305Magnesium 1.
METAL305Magnesium 2.
METAL307Magnesium 2.
BINDING133ATP.
BINDING241ATP; via amide nitrogen.
BINDING244Substrate.
General annotation
Function
Required for high-level resistance to glycopeptide antibiotics. D-Ala--D-Ala ligase of altered specificity which catalyzes ester bond formation between D-Ala and various D-hydroxy acids; produces a peptidoglycan which does not terminate in D-alanine but in D-lactate, thus preventing vancomycin or teicoplanin binding
Catalytic activity
D-alanine + (R)-lactate + ATP = D-alanyl-(R)-lactate + ADP + phosphate
Cofactor
Binds 2 magnesium or manganese ions per subunit (By similarity)
Sequence similarities
Belongs to the D-alanine--D-alanine ligase family
Contains 1 ATP-grasp domain
Reference
P25051 Enterococcus faecium (Streptococcus faecium).
8380148
Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. (J Bacteriol. 1993)
1998664
Identification of vancomycin resistance protein VanA as a D-alanine:D-alanine ligase of altered substrate specificity. (Biochemistry. 1991)
1931965
Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. (Biochemistry. 1991)
1522072
The cytoplasmic peptidoglycan precursor of vancomycin-resistant Enterococcus faecalis terminates in lactate. (J Bacteriol. 1992)
10908650
The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA). (Proc Natl Acad Sci U S A. 2000)



Related Function

Function name
Vancomycin resistance (via D-Ala-D-Lac precursor)

CDS

Data Download
Scientific name NBRC No. CDS Product name
Amycolatopsis azurea14573C791_3573Vancomycin Teicoplanin A-type resistance protein VanA
Amycolatopsis mediterranei13415RAM_42565D-alanine--D-lactate ligase
Catenulispora acidiphila102108Caci_5793D-alanine/D-alanine ligase
Conexibacter woesei100937Cwoe_1414D-alanine/D-alanine ligase
Kribbella flavida14399Kfla_3620D-alanine/D-alanine ligase
Ktedonobacter racemiferKrac_9315D-alanine/D-alanine ligase
Saccharothrix espanaensis15066BN6_49760putative D-alanine-D-lactate ligase
Stackebrandtia nassauensis102104Snas_5356D-alanine/D-alanine ligase
Streptomyces sviceus13980SSEG_10121D-alanine:D-lactate ligase
Tsukamurella paurometabola16120Tpau_0523D-alanine/D-alanine ligase