2CBZ

Structure of the human Multidrug Resistance Protein 1 Nucleotide Binding Domain 1

2CBZ の概要

• エントリーDOI: 10.2210/pdb2cbz/pdb
• 分子名称: MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 1, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: abc proteins, mrp1/abcc1, nucleotide-binding domain, atp-binding, hydrolysis, transport
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26433.03

構造登録者

Ramaen, O.,Leulliot, N.,Sizun, C.,Ulryck, N.,Pamlard, O.,Lallemand, J.-Y.,van Tilbeurgh, H.,Jacquet, E. (登録日: 2006-01-10, 公開日: 2006-05-17, 最終更新日: 2023-12-13)

主引用文献

Ramaen, O.,Leulliot, N.,Sizun, C.,Ulryck, N.,Pamlard, O.,Lallemand, J.-Y.,Van Tilbeurgh, H.,Jacquet, E.
Structure of the Human Multidrug Resistance Protein 1 Nucleotide Binding Domain 1 Bound to Mg(2+)/ATP Reveals a Non-Productive Catalytic Site.
J.Mol.Biol., 359:940-, 2006

PubMed Abstract: 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.

PubMed: 16697012
DOI: 10.1016/J.JMB.2006.04.005

実験手法

X-RAY DIFFRACTION (1.5 Å)