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2.A.66.1.2
Drug:Na+ antiporter, VcmA (exports norfloxacin, ciprofloxacin, ofloxacin, daunomycin, doxorubicin, streptomycin, kanamycin, ethidium, 4',6'-diamidino-2-phenylindole, Hoechst 33342 and acriflavin). The 3-d x-ray structure (3.65Å resolution) is available (He et al., 2010). Ion binding and internal hydration have been studied by molecular dynamics simulations (Vanni et al., 2012).  NorM simultaneously couples drug export to the sodium-motive force and the proton-motive force. Residues involved and protein regions that play important roles in Na+ or H+ binding have been identified (Jin et al. 2014). Na+- and H+-driven conformational changes are facilitated by a network of polar residues in the N-terminal domain cavity, whereas conserved carboxylates buried in the C-terminal domain are critical for stabilizing the drug-bound state. These results establish the role of ion-coupled conformational dynamics in the functional cycle and implicate H+ in the doxorubicin release mechanism (Claxton et al. 2018).

Accession Number:Q9KRU4
Protein Name:VcmA aka NorM aka VC1540
Length:457
Molecular Weight:49424.00
Species:Vibrio cholerae [666]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell inner membrane1 / Multi-pass membrane protein2
Substrate Na+, norfloxacin, Ciprofloxacin, Ofloxacin, Daunomycin, doxorubicin, Streptomycin, Kanamycin, ethidium, 4',6'-diamidino-2-phenylindole, acriflavin, Hoechst 33342

Cross database links:

HEGENOM: HBG479615
RefSeq: NP_231180.2   
Entrez Gene ID: 2613919   
Pfam: PF01554   
KEGG: vch:VC1540   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015297 F:antiporter activity
GO:0015238 F:drug transmembrane transporter activity
GO:0006855 P:drug transmembrane transport
GO:0046677 P:response to antibiotic
GO:0006814 P:sodium ion transport

References (2)

[1] “Na+-driven multidrug efflux pump VcmA from Vibrio cholerae non-O1, a non-halophilic bacterium.”  Huda M.N.et.al.   11583854
[2] “DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.”  Heidelberg J.F.et.al.   10952301
Structure:
3mkt     

External Searches:

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  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MHRYKKEASN LIKLATPVLI ASVAQTGMGF VDTIMAGGVS AIDMAAVSIA ASIWLPSILF 
61:	GVGLLMALVP VVAQLNGAGR QHKIPFEVHQ GLILALLVSV PIIAVLFQTQ FIIRFMDVEE 
121:	AMATKTVGYM HAVIFAVPAY LLFQALRSFT DGMSLTKPAM VIGFIGLLLN IPLNWIFVYG 
181:	KFGAPELGGV GCGVATAIVY WIMLLLLLFY IVTSKRLAHV KVFETFHKPQ PKELIRLFRL 
241:	GFPVAAALFF EVTLFAVVAL LVAPLGSTVV AAHQVALNFS SLVFMFPMSI GAAVSIRVGH 
301:	KLGEQDTKGA AIAANVGLMT GLATACITAL LTVLFREQIA LLYTENQVVV ALAMQLLLFA 
361:	AIYQCMDAVQ VVAAGSLRGY KDMTAIFHRT FISYWVLGLP TGYILGMTNW LTEQPLGAKG 
421:	FWLGFIIGLS AAALMLGQRL YWLQKQSDDV QLHLAAK