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Eur J Med Chem. 2008 Nov;43(11):2557-67. doi: 10.1016/j.ejmech.2008.01.015. Epub 2008 Jan 25.

A molecular model of a putative substrate releasing conformation of multidrug resistance protein 5 (MRP5).

Author information

1
Department of Pharmacology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, MH-Building, Breivika, N-9037 Tromsø, Norway.

Abstract

The ATP-binding cassette (ABC) transporter multidrug resistance protein 5 (MRP5) contributes to the cellular export of organic anions, including guanosine 3'-5' cyclic monophosphate (cGMP). The structural knowledge of this protein is limited, and in lack of an MRP5 X-ray structure, a model of MRP5 was constructed based on the homology with the bacterial ABC transporter Sav1866 from Staphylococcus aureus, which has been crystallised in an outward-facing, substrate releasing conformation. Two putative binding sites were identified, and docking of cGMP indicated that TMHs 1-3, 6, 11 and 12 were in contact with the ligands in binding site 1, while TMHs 1, 3, 5-8 were in contact with the ligands in binding site 2. The proposed MRP5 model may be used for further experimental studies of the molecular structure and function of this member of the ABC-transporter superfamily.

PMID:
18313803
DOI:
10.1016/j.ejmech.2008.01.015
[Indexed for MEDLINE]

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