TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


2.A.1.2.6
(Benomyl, cycloheximide, methotrexate, fluconazole, etc.):H+ antiporter, CaMDR1 (Basso et al., 2010; Cannon et al., 1998). MDR1 catalyzes efflux of commonly used azoles. The central cytoplasmic loop is critical for MDR function, but does not impart substrate specificity (Mandal et al., 2012). The structural basis for polyspecificity of MDR MFS transporters, based on studies with Mdr1, is the extended capacity brought by residues located at the periphery of a binding core to accomodate compounds differing in size and type (Redhu et al. 2018). Each domain in the protein is arranged in a pseudo-symmetric fold of two tandems of 3-TMSs that alternatly expose the drug-binding site towards the inside or the outside of the yeast to promote drug binding and release. Sharma et al. 2022 provided information on these motifs by having screened a library of 64 drug transport-deficient mutants and their corresponding suppressors spontaneously addressing the deficiency. They found that five strains recovered the drug-resistance capacity by expressing CaMdr1 with a secondary mutation. The pairs of debilitating/rescuing residues are distributed either in the same TMS or 3-TMS repeat, at the hinge of 3-TMS repeat tandems, and between the N- and C-domains. Most of these mutants belong to different signature motifs, highlighting a mechanistic role and interplay thought to be conserved among MFS proteins. Results point to the specific role of TMS 11 in the interplay between the N- and C-domains in the inward- to outward-open conformational transition (Sharma et al. 2022).

Accession Number:P28873
Protein Name:BMRP aka CaMDR1 aka MDR1 aka BMR
Length:564
Molecular Weight:62930.00
Species:Candida albicans (Yeast) [5476]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate methotrexate, cycloheximide, benomyl, drug, fluconazole

Cross database links:

Pfam: PF07690   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0015238 F:drug transmembrane transporter activity
GO:0015893 P:drug transport
GO:0046677 P:response to antibiotic
GO:0055085 P:transmembrane transport

References (4)

[1] “Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate.”  Fling M.E.et.al.   2062311
[2] “Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate.”  Fling M.E.et.al.   2062311
[3] “Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate.”  Fling M.E.et.al.   2062311
[4] “Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate.”  Fling M.E.et.al.   2062311

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MHYRFLRDSF VGRVTYHLSK HKYFAHPEEA KNYIIPEKYL ADYKPTLADD TSINFEKEEI 
61:	DNQGEPNSSQ SSSSNNTIVD NNNNNNNDVD GDKIVVTWDG DDDPENPQNW PTLQKAFFIF 
121:	QISFLTTSVY MGSAVYTPGI EELMHDFGIG RVVATLPLTL FVIGYGVGPL VFSPMSENAI 
181:	FGRTSIYIIT LFLFVILQIP TALVNNIAGL CILRFLGGFF ASPCLATGGA SVADVVKFWN 
241:	LPVGLAAWSL GAVCGPSFGP FFGSILTVKA SWRWTFWFMC IISGFSFVML CFTLPETFGK 
301:	TLLYRKAKRL RAITGNDRIT SEGEIENSKM TSHELIIDTL WRPLEITVME PVVLLINIYI 
361:	AMVYSILYLF FEVFPIYFVG VKHFTLVELG TTYMSIVIGI VIAAFIYIPV IRQKFTKPIL 
421:	RQEQVFPEVF IPIAIVGGIL LTSGLFIFGW SANRTTHWVG PLFGAATTAS GAFLIFQTLF 
481:	NFMGASFKPH YIASVFASND LFRSVIASVF PLFGAPLFDN LATPEYPVAW GSSVLGFITL 
541:	VMIAIPVLFY LNGPKLRARS KYAN