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Protein

D-alanyl-D-alanine dipeptidase

Gene

vanX

Organism
Enterococcus faecium (Streptococcus faecium)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes hydrolysis of the D-alanyl-D-alanine dipeptide.UniRule annotation2 Publications

Catalytic activityi

D-Ala-D-Ala + H2O = 2 D-Ala.UniRule annotation2 Publications

Cofactori

Zn2+UniRule annotation2 Publications, Fe2+UniRule annotation2 Publications, Co2+UniRule annotation2 Publications, Ni2+UniRule annotation2 PublicationsNote: Binds 1 zinc ion per subunit. Can also be activated by other divalent cations such as iron, cobalt, or nickel.UniRule annotation2 Publications

Enzyme regulationi

Inhibited by aminoalkyl phosphinate analogs.1 Publication

Kineticsi

Kcat is 4.7 sec(-1) with D-Ala-D-Ala. Kcat is 1.8 sec(-1) with D-Ala-D-Ser. Kcat is 0.35 sec(-1) with D-Ser-D-Ala. Kcat is 0.005 sec(-1) with D-Ala-D-lactate.

  1. KM=1 mM for D-Ala-D-Ala (in the absence of divalent cations)1 Publication
  2. KM=2.8 mM for D-Ala-D-Ser KM=1.7 mM for D-Ser-D-Ala Vmax=12.3 nmol/min/µg enzyme with D-Ala-D-Ala as substrate1 Publication
  1. Vmax=4.7 nmol/min/µg enzyme with D-Ala-D-Ser as substrate1 Publication
  2. Vmax=1.3 nmol/min/µg enzyme with D-Ser-D-Ala as substrate1 Publication

pH dependencei

Optimum pH is 7-9.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei71 – 711Transition state stabilizerCurated
Metal bindingi116 – 1161Zinc; via tele nitrogen; catalyticUniRule annotation1 Publication
Metal bindingi123 – 1231Zinc; catalyticUniRule annotation1 Publication
Active sitei181 – 1811Proton donor/acceptor1 Publication
Metal bindingi184 – 1841Zinc; via pros nitrogen; catalyticUniRule annotation1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Antibiotic resistance, Cell wall biogenesis/degradation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-15475.
BRENDAi3.4.13.22. 2096.
SABIO-RKQ06241.

Protein family/group databases

MEROPSiM15.011.

Names & Taxonomyi

Protein namesi
Recommended name:
D-alanyl-D-alanine dipeptidaseUniRule annotation (EC:3.4.13.22UniRule annotation)
Short name:
D-Ala-D-Ala dipeptidaseUniRule annotation
Alternative name(s):
Vancomycin B-type resistance protein VanX
Gene namesi
Name:vanX
Encoded oniPlasmid pIP8160 Publication
OrganismiEnterococcus faecium (Streptococcus faecium)
Taxonomic identifieri1352 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesEnterococcaceaeEnterococcus

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL1681622.
DrugBankiDB00512. Vancomycin.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 202202D-alanyl-D-alanine dipeptidasePRO_0000217840Add
BLAST

Expressioni

Inductioni

By vancomycin, mediated by VanS/VanR.1 Publication

Interactioni

Subunit structurei

Homodimer.2 Publications

Chemistry

BindingDBiQ06241.

Structurei

Secondary structure

1
202
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 73Combined sources
Helixi8 – 103Combined sources
Helixi20 – 223Combined sources
Beta strandi37 – 393Combined sources
Beta strandi41 – 433Combined sources
Helixi44 – 5613Combined sources
Beta strandi59 – 6810Combined sources
Helixi73 – 8311Combined sources
Helixi92 – 954Combined sources
Beta strandi97 – 993Combined sources
Helixi103 – 1064Combined sources
Beta strandi108 – 1103Combined sources
Helixi115 – 1184Combined sources
Beta strandi121 – 1288Combined sources
Turni129 – 1313Combined sources
Helixi146 – 1483Combined sources
Beta strandi153 – 1553Combined sources
Helixi157 – 17115Combined sources
Turni172 – 1743Combined sources
Beta strandi175 – 1773Combined sources
Beta strandi184 – 1896Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1R44X-ray2.25A/B/C/D/E/F1-202[»]
ProteinModelPortaliQ06241.
SMRiQ06241. Positions 1-202.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ06241.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M15D family.UniRule annotation

Phylogenomic databases

KOiK08641.

Family and domain databases

Gene3Di3.30.1380.10. 1 hit.
HAMAPiMF_01924. A_A_dipeptidase.
InterProiIPR000755. A_A_dipeptidase.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
[Graphical view]
PfamiPF01427. Peptidase_M15. 1 hit.
[Graphical view]
PIRSFiPIRSF026671. AA_dipeptidase. 1 hit.
SUPFAMiSSF55166. SSF55166. 1 hit.

Sequencei

Sequence statusi: Complete.

Q06241-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEIGFTFLDE IVHGVRWDAK YATWDNFTGK PVDGYEVNRI VGTYELAESL
60 70 80 90 100
LKAKELAATQ GYGLLLWDGY RPKRAVNCFM QWAAQPENNL TKESYYPNID
110 120 130 140 150
RTEMISKGYV ASKSSHSRGS AIDLTLYRLD TGELVPMGSR FDFMDERSHH
160 170 180 190 200
AANGISCNEA QNRRRLRSIM ENSGFEAYSL EWWHYVLRDE PYPNSYFDFP

VK
Length:202
Mass (Da):23,380
Last modified:October 1, 1994 - v1
Checksum:i649C00927D08669C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97297 Genomic DNA. Translation: AAA65957.1.
PIRiS72342.
RefSeqiWP_000402347.1. NZ_LNMX01000005.1.
YP_001019034.1. NC_008821.1.
YP_001974795.1. NC_010980.1.
YP_002128400.1. NC_011140.1.
YP_976076.1. NC_008768.1.

Genome annotation databases

GeneIDi4670250.
4783136.
6385878.
6779646.
KEGGiag:AAA65957.
pg:4670250.
pg:4783136.
pg:6385878.
pg:6779646.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97297 Genomic DNA. Translation: AAA65957.1.
PIRiS72342.
RefSeqiWP_000402347.1. NZ_LNMX01000005.1.
YP_001019034.1. NC_008821.1.
YP_001974795.1. NC_010980.1.
YP_002128400.1. NC_011140.1.
YP_976076.1. NC_008768.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1R44X-ray2.25A/B/C/D/E/F1-202[»]
ProteinModelPortaliQ06241.
SMRiQ06241. Positions 1-202.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiQ06241.
ChEMBLiCHEMBL1681622.
DrugBankiDB00512. Vancomycin.

Protein family/group databases

MEROPSiM15.011.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi4670250.
4783136.
6385878.
6779646.
KEGGiag:AAA65957.
pg:4670250.
pg:4783136.
pg:6385878.
pg:6779646.

Phylogenomic databases

KOiK08641.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-15475.
BRENDAi3.4.13.22. 2096.
SABIO-RKQ06241.

Miscellaneous databases

EvolutionaryTraceiQ06241.

Family and domain databases

Gene3Di3.30.1380.10. 1 hit.
HAMAPiMF_01924. A_A_dipeptidase.
InterProiIPR000755. A_A_dipeptidase.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
[Graphical view]
PfamiPF01427. Peptidase_M15. 1 hit.
[Graphical view]
PIRSFiPIRSF026671. AA_dipeptidase. 1 hit.
SUPFAMiSSF55166. SSF55166. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: BM4147.
    Transposon: Tn1546.
  2. "Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147."
    Wu Z., Wright G.D., Walsh C.T.
    Biochemistry 34:2455-2463(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-10, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
  3. "The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147."
    Arthur M., Molinas C., Courvalin P.
    J. Bacteriol. 174:2582-2591(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
    Strain: BM4147.
  4. "Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine."
    Reynolds P.E., Depardieu F., Dutka-Malen S., Arthur M., Courvalin P.
    Mol. Microbiol. 13:1065-1070(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY.
  5. "The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance."
    Bussiere D.E., Pratt S.D., Katz L., Severin J.M., Holzman T., Park C.H.
    Mol. Cell 2:75-84(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH ZINC, COFACTOR, SUBUNIT, ACTIVE SITE.

Entry informationi

Entry nameiVANX_ENTFC
AccessioniPrimary (citable) accession number: Q06241
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: May 11, 2016
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Does not hydrolyze D-Ala-D-lactate, which remains intact for subsequent incorporation into peptidoglycan precursors. Production of precursors ending in D-Ala-D-lactate instead of D-Ala-D-Ala decreases affinity of vancomycin for the peptidoglycan chain and leads to vancomycin resistance (PubMed:7873524).1 Publication

Keywords - Technical termi

3D-structure, Direct protein sequencing, Plasmid

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.