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P25051 (VANA_ENTFC) Reviewed, UniProtKB/Swiss-Prot

Last modified October 19, 2011. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Vancomycin/teicoplanin A-type resistance protein VanA
EC=6.1.2.1
Alternative name(s):
D-alanine--D-lactate ligase
VanA ligase
Gene names
Name:vanA
Encoded onPlasmid pIP816
OrganismEnterococcus faecium (Streptococcus faecium)
Taxonomic identifier1352 [NCBI]
Taxonomic lineageBacteria › Firmicutes › Lactobacillales › Enterococcaceae › Enterococcus

Protein attributes

Sequence length343 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3

Catalytic activity

D-alanine + (R)-lactate + ATP = D-alanyl-(R)-lactate + ADP + phosphate. Ref.3

Cofactor

Binds 2 magnesium or manganese ions per subunit By similarity.

Subcellular location

Cell membrane; Peripheral membrane protein; Cytoplasmic side HAMAP MF_00047.

Induction

By vancomycin, mediated by VanS/VanR. HAMAP MF_00047

Sequence similarities

Belongs to the D-alanine--D-alanine ligase family.

Contains 1 ATP-grasp domain.

Biophysicochemical properties

Kinetic parameters:

KM=7.1 mM for D-lactate Ref.3

KM=3.8 mM for D-alanine

KM=0.6 mM for 2-hydroxybutyrate

KM=3.2 mM for 2-hydroxyvalerate

KM=11 mM for 2-hydroxycaproate

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 343343Vancomycin/teicoplanin A-type resistance protein VanA HAMAP MF_00047
PRO_0000177917

Regions

Domain137 – 338202ATP-grasp
Nucleotide binding169 – 1713ATP HAMAP MF_00047
Nucleotide binding177 – 1782ATP HAMAP MF_00047
Nucleotide binding207 – 2148ATP HAMAP MF_00047
Nucleotide binding304 – 3052ATP HAMAP MF_00047

Sites

Metal binding3051Magnesium 1
Metal binding3051Magnesium 2
Metal binding3071Magnesium 2
Binding site1331ATP
Binding site2411ATP; via amide nitrogen
Binding site2441Substrate

Secondary structure

1 .................................................................. 343
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P25051 [UniParc].

Last modified May 1, 1992. Version 1.
Checksum: AAA48E3B2AD48E03

FASTA34337,443
        10         20         30         40         50         60 
MNRIKVAILF GGCSEEHDVS VKSAIEIAAN INKEKYEPLY IGITKSGVWK MCEKPCAEWE 

        70         80         90        100        110        120 
NDNCYSAVLS PDKKMHGLLV KKNHEYEINH VDVAFSALHG KSGEDGSIQG LFELSGIPFV 

       130        140        150        160        170        180 
GCDIQSSAIC MDKSLTYIVA KNAGIATPAF WVINKDDRPV AATFTYPVFV KPARSGSSFG 

       190        200        210        220        230        240 
VKKVNSADEL DYAIESARQY DSKILIEQAV SGCEVGCAVL GNSAALVVGE VDQIRLQYGI 

       250        260        270        280        290        300 
FRIHQEVEPE KGSENAVITV PADLSAEERG RIQETAKKIY KALGCRGLAR VDMFLQDNGR 

       310        320        330        340 
IVLNEVNTLP GFTSYSRYPR MMAAAGIALP ELIDRLIVLA LKG

« Hide

References

[1]"The VANA glycopeptide resistance protein is related to D-alanyl-D-alanine ligase cell wall biosynthesis enzymes."
Dutka-Malen S., Molinas C., Arthur M., Courvalin P.
Mol. Gen. Genet. 224:364-372(1990) [PubMed: 2266943] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-9.
Strain: BM4147.
[2]"Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147."
Arthur M., Molinas C., Depardieu F., Courvalin P.
J. Bacteriol. 175:117-127(1993) [PubMed: 8380148] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: BM4147.
[3]"Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA."
Bugg T.D.H., Wright G.D., Dutka-Malen S., Arthur M., Courvalin P., Walsh C.T.
Biochemistry 30:10408-10415(1991) [PubMed: 1931965] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
Strain: BM4147.
[4]"The cytoplasmic peptidoglycan precursor of vancomycin-resistant Enterococcus faecalis terminates in lactate."
Handwerger S., Pucci M.J., Volk K.J., Liu J., Lee M.S.
J. Bacteriol. 174:5982-5984(1992) [PubMed: 1522072] [Abstract]
Cited for: CHARACTERIZATION OF REACTION PRODUCT.
[5]"The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA)."
Roper D.I., Huyton T., Vagin A., Dodson G.
Proc. Natl. Acad. Sci. U.S.A. 97:8921-8925(2000) [PubMed: 10908650] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH MAGNESIUM; ADP AND INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X56895 Genomic DNA. Translation: CAA40215.1.
M97297 Genomic DNA. Translation: AAA65956.1.
PIRCESOVM. S12254.
RefSeqYP_001019035.1. NC_008821.1.
YP_001974796.1. NC_010980.1.
YP_002128399.1. NC_011140.1.
YP_976077.1. NC_008768.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1E4EX-ray2.50A/B1-343[»]
ProteinModelPortalP25051.
SMRP25051. Positions 2-342.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID4670249.
4783144.
6385877.
6779647.

Phylogenomic databases

ProtClustDBPRK14568.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-15466.

Family and domain databases

HAMAPMF_00047. Dala_Dala_lig. Divergent sequence.
[Tree]
InterProIPR011761. 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.
IPR013817. Pre-ATP_grasp.
IPR016185. PreATP-grasp-like.
[Graphical view]
Gene3DG3DSA:3.30.1490.20. ATP_grasp_subdomain_1. 1 hit.
G3DSA:3.30.470.20. ATP_grasp_subdomain_2. 1 hit.
G3DSA:3.40.50.20. Pre-ATP_grasp. 1 hit.
PANTHERPTHR23132. PTHR23132. 1 hit.
PfamPF07478. Dala_Dala_lig_C. 1 hit.
PF01820. Dala_Dala_lig_N. 1 hit.
[Graphical view]
SUPFAMSSF52440. PreATP-grasp-like. 1 hit.
TIGRFAMsTIGR01205. D_ala_D_alaTIGR. 1 hit.
PROSITEPS50975. ATP_GRASP. 1 hit.
PS00843. DALA_DALA_LIGASE_1. 1 hit.
PS00844. DALA_DALA_LIGASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameVANA_ENTFC
AccessionPrimary (citable) accession number: P25051
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: October 19, 2011
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents