8hw2 | pdb_00008hw2

Cryo-EM structure of beta-estradiol 17-(beta-D-glucuronide)-bound human ABC transporter ABCC3 in nanodiscs

Structural highlights

8hw2 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.65Å
Ligands:	U38
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MRP3_HUMAN ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:11581266, PubMed:15083066, PubMed:10359813). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:15083066, PubMed:11581266). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:11581266, PubMed:10359813).[UniProtKB:O88563]^[1] ^[2] ^[3] ^[4]

References

↑ Kool M, van der Linden M, de Haas M, Scheffer GL, de Vree JM, Smith AJ, Jansen G, Peters GJ, Ponne N, Scheper RJ, Elferink RP, Baas F, Borst P. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6914-9. PMID:10359813 doi:10.1073/pnas.96.12.6914
↑ Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7. PMID:11581266 doi:10.1074/jbc.M107041200
↑ Lee YM, Cui Y, König J, Risch A, Jäger B, Drings P, Bartsch H, Keppler D, Nies AT. Identification and functional characterization of the natural variant MRP3-Arg1297His of human multidrug resistance protein 3 (MRP3/ABCC3). Pharmacogenetics. 2004 Apr;14(4):213-23. PMID:15083066 doi:10.1097/00008571-200404000-00001
↑ Hau RK, Klein RR, Wright SH, Cherrington NJ. Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier. Drug Metab Dispos. 2022 Jun;50(6):770-780. PMID:35307651 doi:10.1124/dmd.121.000748

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OCA

[1] Kool M, van der Linden M, de Haas M, Scheffer GL, de Vree JM, Smith AJ, Jansen G, Peters GJ, Ponne N, Scheper RJ, Elferink RP, Baas F, Borst P. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6914-9. PMID:10359813 doi:10.1073/pnas.96.12.6914

[2] Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7. PMID:11581266 doi:10.1074/jbc.M107041200

[3] Lee YM, Cui Y, König J, Risch A, Jäger B, Drings P, Bartsch H, Keppler D, Nies AT. Identification and functional characterization of the natural variant MRP3-Arg1297His of human multidrug resistance protein 3 (MRP3/ABCC3). Pharmacogenetics. 2004 Apr;14(4):213-23. PMID:15083066 doi:10.1097/00008571-200404000-00001

[4] Hau RK, Klein RR, Wright SH, Cherrington NJ. Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier. Drug Metab Dispos. 2022 Jun;50(6):770-780. PMID:35307651 doi:10.1124/dmd.121.000748

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8hw2 | pdb_00008hw2

Cryo-EM structure of beta-estradiol 17-(beta-D-glucuronide)-bound human ABC transporter ABCC3 in nanodiscs

Structural highlights

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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