[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-9. STRAIN=BM4147; DOI=10.1007/BF00262430; PubMed=2266943 [NCBI, ExPASy, EBI, Israel, Japan] Dutka-Malen S., Molinas C., Arthur M., Courvalin P.; "The VANA glycopeptide resistance protein is related to D-alanyl-D-alanine ligase cell wall biosynthesis enzymes."; Mol. Gen. Genet. 224:364-372(1990).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. STRAIN=BM4147; PubMed=8380148 [NCBI, ExPASy, EBI, Israel, Japan] Arthur M., Molinas C., Depardieu F., Courvalin P.; "Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147."; J. Bacteriol. 175:117-127(1993).
[3]	CHARACTERIZATION. STRAIN=BM4147; DOI=10.1021/bi00107a007; PubMed=1931965 [NCBI, ExPASy, EBI, Israel, Japan] Bugg T.D.H., Wright G.D., Dutka-Malen S., Arthur M., Courvalin P., Walsh C.T.; "Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA."; Biochemistry 30:10408-10415(1991).
[4]	CHARACTERIZATION. PubMed=1522072 [NCBI, ExPASy, EBI, Israel, Japan] Handwerger S., Pucci M.J., Volk K.J., Liu J., Lee M.S.; "The cytoplasmic peptidoglycan precursor of vancomycin-resistant Enterococcus faecalis terminates in lactate."; J. Bacteriol. 174:5982-5984(1992).

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.
COFACTOR: Binds 2 magnesium or manganese ions per subunit (By similarity).
SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side.
INDUCTION: By vancomycin, mediated by vanS/vanR.
SIMILARITY: Belongs to the D-alanine--D-alanine ligase family.
SIMILARITY: Contains 1 ATP-grasp domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X56895; CAA40215.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M97297; AAA65956.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S12254; CESOVM.

RefSeq

YP_001019035.1; -.
YP_001974796.1; -.
YP_002128399.1; -.
YP_976077.1; -.

3D structure databases

PDB

1E4E; X-ray; 2.50 A; A/B=1-343.

[ExPASy / RCSB / EBI]

PDBsum

1E4E; -.

ModBase

P25051.

Ontologies

GO:0005618;	Cellular component: cell wall (inferred from electronic annotation from InterPro).
GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from HAMAP).
GO:0005886;	Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0008716;	Molecular function: D-alanine-D-alanine ligase activity (inferred from electronic annotation from HAMAP).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0030145;	Molecular function: manganese ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0009252;	Biological process: peptidoglycan biosynthetic process (inferred from electronic annotation from HAMAP).
GO:0008360;	Biological process: regulation of cell shape (inferred from electronic annotation from UniProtKB-KW).
GO:0046677;	Biological process: response to antibiotic (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

HAMAP

MF_00047; atypical; 1.
PBIL [Tree]

InterPro

IPR011761; ATP-grasp.
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.
Graphical view of domain structure.

Gene3D

G3DSA:3.30.470.20; ATP_grasp_subdomain_2; 1.
G3DSA:3.40.50.20; Pre-ATP_grasp; 1.

Pfam

PF07478; Dala_Dala_lig_C; 1.
PF01820; Dala_Dala_lig_N; 1.
Pfam graphical view of domain structure.

TIGRFAMs

TIGR01205; D_ala_D_alaTIGR; 1.

PROSITE

PS50975; ATP_GRASP; 1.
PS00843; DALA_DALA_LIGASE_1; 1.
PS00844; DALA_DALA_LIGASE_2; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

GeneID

4670249; -.
4783144; -.
6385877; -.
6779647; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Antibiotic resistance; ATP-binding; Cell membrane; Cell shape; Cell wall biogenesis/degradation; Cytoplasm; Direct protein sequencing; Ligase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; Peptidoglycan synthesis; Plasmid.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 343`	`343`	`Vancomycin/teicoplanin A-type resistance protein vanA.`	`PRO_0000177917`
`DOMAIN`	`137 338`	`202`	`ATP-grasp.`
`NP_BIND`	`163 216`	`54`	`ATP (By similarity).`
`METAL`	`292 292`		`Magnesium or manganese 1 (By similarity).`
`METAL`	`305 305`		`Magnesium or manganese 1 (By similarity).`
`METAL`	`305 305`		`Magnesium or manganese 2 (By similarity).`
`METAL`	`307 307`		`Magnesium or manganese 2 (By similarity).`
`STRAND`	`4 11`	`8`
`HELIX`	`17 30`	`14`
`TURN`	`33 35`	`3`
`STRAND`	`36 43`	`8`
`STRAND`	`49 53`	`5`
`STRAND`	`65 69`	`5`
`TURN`	`73 75`	`3`
`STRAND`	`77 82`	`6`
`STRAND`	`85 90`	`6`
`STRAND`	`92 96`	`5`
`TURN`	`101 103`	`3`
`STRAND`	`104 106`	`3`
`HELIX`	`107 115`	`9`
`STRAND`	`119 121`	`3`
`HELIX`	`124 131`	`8`
`HELIX`	`133 142`	`10`
`STRAND`	`150 153`	`4`
`HELIX`	`161 163`	`3`
`STRAND`	`168 174`	`7`
`TURN`	`177 180`	`4`
`STRAND`	`182 184`	`3`
`HELIX`	`187 189`	`3`
`HELIX`	`190 197`	`8`
`TURN`	`198 200`	`3`
`STRAND`	`202 208`	`7`
`STRAND`	`212 222`	`11`
`STRAND`	`232 239`	`8`
`HELIX`	`243 245`	`3`
`STRAND`	`246 248`	`3`
`HELIX`	`249 251`	`3`
`STRAND`	`254 258`	`5`
`HELIX`	`266 282`	`17`
`STRAND`	`286 295`	`10`
`STRAND`	`301 309`	`9`
`HELIX`	`317 324`	`8`
`HELIX`	`329 341`	`13`

Sequence information

Length: 343 AA [This is the length of the unprocessed precursor]

Molecular weight: 37443 Da [This is the MW of the unprocessed precursor]

CRC64: AAA48E3B2AD48E03 [This is a checksum on the sequence]

        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

P25051 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools