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2.A.6.5.5
Mycobacterial heme acquisition system, Rv0202c - Rv0207c. Takes up free heme and heme from hemoglobin as an iron source together with the secreted protein, Rv0203 (O53654) (Owens et al. 2013). May function with Rv0206c (MmpL3; TC#2.A.6.5.6) and Rv0202c (Tullius et al., 2011). However, see description of MmpL3 (2.A.6.5.6).  These two proteins are targets of drug action (Owens et al. 2013). A 12 TMS topology has been suggested (Belardinelli and Jackson 2017). Mycobacterial membrane protein Large 3 (MmpL3) is a promising drug target because its activity is essential and required for cell-wall biosynthesis. Several classes of MmpL3 inhibitors have been developed against Mycobacterium tuberculosis (Mtb) with potent anti-TB activity, one of which is the drug candidate SQ109. Yang et al. 2020 have determined crystal structures of MmpL3 in complex with NITD-349 and SPIRO. Both inhibitors bind deep in the central channel of the transmembrane (TM) domain and cause conformational changes to the protein. The amide nitrogen and indole nitrogen of NITD-349 and the piperidine nitrogen of SPIRO interact and clamp Asp645. Analysis of the two structures reveals that these inhibitors target the proton relay pathway to block the activity of MmpL3 (Yang et al. 2020).

Accession Number:P65374
Protein Name:Putative membrane protein mmpL11
Length:966
Molecular Weight:103502.00
Species:Mycobacterium tuberculosis [1773]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate ferroheme b

Cross database links:

Entrez Gene ID: 886750    923105   
Pfam: PF03176   
KEGG: mtc:MT0212    mtu:Rv0202c   

Gene Ontology

GO:0005618 C:cell wall
GO:0005829 C:cytosol
GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane

References (2)

[1] “Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.”  Cole S.T.et.al.   9634230
[2] “Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains.”  Fleischmann R.D.et.al.   12218036

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MMRLSRNLRR CRWLVFTGWL LALVPAVYLA MTQSGNLTGG GFEVAGSQSL LVHDQLDAHY 
61:	PDRGAPALAL VAAPRPDASY QDIDNAVALL RQIASELPGV TEAPNPTQRP PQPDRPYVVS 
121:	LRLDARNAGT SDVAKKLRDR IGVKGDQSGQ TANGKVRLYV IGQGALSAAA AANTKHDIAN 
181:	AERWNLPIIL MVLVAVFGSL AAAAIPLALA VCTVVITMGL VFVLSMHTTM SVFVTSTVSM 
241:	FGIALAVDYS LFILMRYREE LRCGRRPPDA VDAAMATSGL AVVLSGMTVI ASLTGIYLIN 
301:	TPALRSMATG AILAVAVAML TSATLTPAVL ATFARAAAKR SALVHWSRRP ASTQSWFWSR 
361:	WVGWVMRRPW ITALAASTVL LVMAAPATLM VLGNSLLRQF DSSHEIRTGA AAAAQALGPG 
421:	ALGPVQVLVR FDAGGASAPE HSQTIAAIRH RIAQAPNVVS VAPPRFADDN GSALLSAVLS 
481:	VDPEDLGARD TITWMRTQLP RVAGAAQVDV GGPTALIKDF DDRVSATQPL VLVFVAVIAF 
541:	LMLLISIRSV FLAFKGVLMT LLSVAAAYGS LVMVFQWGWA RGLGFPALHS IDSTVPPLVL 
601:	AMTFGLSMDY EIFLLTRIRE RFLQTGQTRD AVAYGVRTSA RTITSAALIM IAVFCGFAFA 
661:	GMPLVAEIGV ACAVAIAVDA TVVRLVLVPA LMAMFDRWNW WLPRWLAHIL PSVDFDRPLP 
721:	KVDLGDVVVI PDDFAAAIPP SADVRMVLKS AAKLKRLAPD AICVTDPLAF TGCGCDGKAL 
781:	DQVQLAYRNG IARAISWGQR PVHPVTVWRK RLAVALDALQ TTTWECGGVQ THRAGPGYRR 
841:	RSPVETTNVA LPTGDRLQIP TGAETLRFKG YLIMSRNSSH DYADFADLVD TMAPETAAAV 
901:	LAGMDRYYSC QAPGRQWMAT QLVGRLADPQ PSDLGDQSPG ADAQAKWEEV RRRCLSVAVA 
961:	MLEEAR