2cbz
From Proteopedia
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==Overview== | ==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. | 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. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Congenital bilateral absence of vas deferens OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602421 602421]], Cystic fibrosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602421 602421]], Earwax, wet/dry OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607040 607040]], Hypertrypsinemia, neonatal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602421 602421]], Pancreatitis, idiopathic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602421 602421]], Sweat chloride elevation without CF OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602421 602421]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transport]] | [[Category: transport]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:13:51 2007'' |
Revision as of 19:07, 12 November 2007
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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 MG and ATP as ligands. Structure known Active Site: AC1. 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
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