2cbz
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Human multidrug resistance protein 1 (MRP1) is a membrane protein that | + | Human multidrug resistance protein 1 (MRP1) is a membrane protein that belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. MRP1 contributes to chemotherapy failure by exporting a wide range of anti-cancer drugs when over expressed in the plasma membrane of cells. Here, we report the first high-resolution crystal structure of human MRP1-NBD1. Drug efflux requires energy resulting from hydrolysis of ATP by nucleotide binding domains (NBDs). Contrary to the prokaryotic NBDs, the extremely low intrinsic ATPase activity of isolated MRP1-NBDs allowed us to obtain the structure of wild-type NBD1 in complex with Mg2+/ATP. The structure shows that MRP1-NBD1 adopts a canonical fold, but reveals an unexpected non-productive conformation of the catalytic site, providing an explanation for the low intrinsic ATPase activity of NBD1 and new hypotheses on the cooperativity of ATPase activity between NBD1 and NBD2 upon heterodimer formation. |
==Disease== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Jacquet, E.]] | [[Category: Jacquet, E.]] | ||
| - | [[Category: Lallemand, J | + | [[Category: Lallemand, J Y.]] |
[[Category: Leulliot, N.]] | [[Category: Leulliot, N.]] | ||
[[Category: Pamlard, O.]] | [[Category: Pamlard, O.]] | ||
[[Category: Ramaen, O.]] | [[Category: Ramaen, O.]] | ||
[[Category: Sizun, C.]] | [[Category: Sizun, C.]] | ||
| - | [[Category: Tilbeurgh, H | + | [[Category: Tilbeurgh, H Van.]] |
[[Category: Ulryck, N.]] | [[Category: Ulryck, N.]] | ||
[[Category: ATP]] | [[Category: ATP]] | ||
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[[Category: transport]] | [[Category: transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:47:04 2008'' |
Revision as of 14:47, 21 February 2008
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STRUCTURE OF THE HUMAN MULTIDRUG RESISTANCE PROTEIN 1 NUCLEOTIDE BINDING DOMAIN 1
Contents |
Overview
Human multidrug resistance protein 1 (MRP1) is a membrane protein that belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. MRP1 contributes to chemotherapy failure by exporting a wide range of anti-cancer drugs when over expressed in the plasma membrane of cells. Here, we report the first high-resolution crystal structure of human MRP1-NBD1. Drug efflux requires energy resulting from hydrolysis of ATP by nucleotide binding domains (NBDs). Contrary to the prokaryotic NBDs, the extremely low intrinsic ATPase activity of isolated MRP1-NBDs allowed us to obtain the structure of wild-type NBD1 in complex with Mg2+/ATP. The structure shows that MRP1-NBD1 adopts a canonical fold, but reveals an unexpected non-productive conformation of the catalytic site, providing an explanation for the low intrinsic ATPase activity of NBD1 and new hypotheses on the cooperativity of ATPase activity between NBD1 and NBD2 upon heterodimer formation.
Disease
Known diseases associated with this structure: Congenital bilateral absence of vas deferens OMIM:[602421], Cystic fibrosis OMIM:[602421], Earwax, wet/dry OMIM:[607040], Hypertrypsinemia, neonatal OMIM:[602421], Pancreatitis, idiopathic OMIM:[602421], Sweat chloride elevation without CF OMIM:[602421]
About this Structure
2CBZ is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site., Ramaen O, Leulliot N, Sizun C, Ulryck N, Pamlard O, Lallemand JY, Tilbeurgh H, Jacquet E, J Mol Biol. 2006 Jun 16;359(4):940-9. Epub 2006 May 2. PMID:16697012
Page seeded by OCA on Thu Feb 21 16:47:04 2008
