3.A.1.201.14 P-glycoprotein-1 MDR exporter. Transports multiple drugs, cancer chemotherapy agents, cancer unrelated compounds and many xenobiotics including ivermectin (Ardelli 2013). The crystal structure at 3.4 A resolution is available (Jin et al. 2012). It has 4,000x higher affinity for actinomycin D in the membrane bilayers than in detergent. A "ball and socket joint" and salt bridges similar to ABC importers suggested that both types of systems, importers and exporters, use the same mechanism to interconnect ATP hydrolysis with transport and achieve alternating access of the substrate binding site to the two sides of the membrane.
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Accession Number: | P34712 |
Protein Name: | Multidrug resistance protein pgp-1 |
Length: | 1321 |
Molecular Weight: | 145063.00 |
Species: | Caenorhabditis elegans [6239] |
Number of TMSs: | 12 |
Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
Substrate |
xenobiotic, ivermectin, drug |
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1: MLRNGSLRQS LRTLDSFSLA PEDVLKTAIK TVEDYEGDNI DSNGEIKITR DAKEEVVNKV
61: SIPQLYRYTT TLEKLLLFIG TLVAVITGAG LPLMSILQGK VSQAFINEQI VINNNGSTFL
121: PTGQNYTKTD FEHDVMNVVW SYAAMTVGMW AAGQITVTCY LYVAEQMNNR LRREFVKSIL
181: RQEISWFDTN HSGTLATKLF DNLERVKEGT GDKIGMAFQY LSQFITGFIV AFTHSWQLTL
241: VMLAVTPIQA LCGFAIAKSM STFAIRETLR YAKAGKVVEE TISSIRTVVS LNGLRYELER
301: YSTAVEEAKK AGVLKGLFLG ISFGAMQASN FISFALAFYI GVGWVHDGSL NFGDMLTTFS
361: SVMMGSMALG LAGPQLAVLG TAQGAASGIY EVLDRKPVID SSSKAGRKDM KIKGDITVEN
421: VHFTYPSRPD VPILRGMNLR VNAGQTVALV GSSGCGKSTI ISLLLRYYDV LKGKITIDGV
481: DVRDINLEFL RKNVAVVSQE PALFNCTIEE NISLGKEGIT REEMVAACKM ANAEKFIKTL
541: PNGYNTLVGD RGTQLSGGQK QRIAIARALV RNPKILLLDE ATSALDAESE GIVQQALDKA
601: AKGRTTIIIA HRLSTIRNAD LIISCKNGQV VEVGDHRALM AQQGLYYDLV TAQTFTDAVD
661: SAAEGKFSRE NSVARQTSEH EGLSRQASEM DDIMNRVRSS TIGSITNGPV IDEKEERIGK
721: DALSRLKQEL EENNAQKTNL FEILYHARPH ALSLFIGMST ATIGGFIYPT YSVFFTSFMN
781: VFAGNPADFL SQGHFWALMF LVLAAAQGIC SFLMTFFMGI ASESLTRDLR NKLFRNVLSQ
841: HIGFFDSPQN ASGKISTRLA TDVPNLRTAI DFRFSTVITT LVSMVAGIGL AFFYGWQMAL
901: LIIAILPIVA FGQYLRGRRF TGKNVKSASE FADSGKIAIE AIENVRTVQA LAREDTFYEN
961: FCEKLDIPHK EAIKEAFIQG LSYGCASSVL YLLNTCAYRM GLALIITDPP TMQPMRVLRV
1021: MYAITISTST LGFATSYFPE YAKATFAGGI IFGMLRKISK IDSLSLAGEK KKLYGKVIFK
1081: NVRFAYPERP EIEILKGLSF SVEPGQTLAL VGPSGCGKST VVALLERFYD TLGGEIFIDG
1141: SEIKTLNPEH TRSQIAIVSQ EPTLFDCSIA ENIIYGLDPS SVTMAQVEEA ARLANIHNFI
1201: AELPEGFETR VGDRGTQLSG GQKQRIAIAR ALVRNPKILL LDEATSALDT ESEKVVQEAL
1261: DRAREGRTCI VIAHRLNTVM NADCIAVVSN GTIIEKGTHT QLMSEKGAYY KLTQKQMTEK
1321: K