4FYH

Crystal structure of rcl with phospho-triciribine

4FYH の概要

• エントリーDOI: 10.2210/pdb4fyh/pdb
• 関連するPDBエントリー: 2KLH 4FYI 4FYK
• 分子名称: Deoxyribonucleoside 5'-monophosphate N-glycosidase, 5-methyl-1-(5-O-phosphono-beta-D-ribofuranosyl)-1,5-dihydro-1,4,5,6,8-pentaazaacenaphthylen-3-amine, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: deoxyribonucleoside 5'-monophosphate n-glycosidase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cytoplasm (By similarity): O35820
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 70774.79

構造登録者

Labesse, G.,Padilla, A.,Kaminski, P.A. (登録日: 2012-07-04, 公開日: 2013-01-02, 最終更新日: 2024-02-28)

主引用文献

Padilla, A.,Amiable, C.,Pochet, S.,Kaminski, P.A.,Labesse, G.
Structure of the oncoprotein Rcl bound to three nucleotide analogues.
Acta Crystallogr.,Sect.D, 69:247-255, 2013

PubMed Abstract: Rcl is a novel N-glycoside hydrolase found in mammals that shows specificity for the hydrolysis of 5'-monophosphate nucleotides. Its role in nucleotide catabolism and the resulting production of 2-deoxyribose 5-phosphate has suggested that it might fuel cancer growth. Its expression is regulated by c-Myc, but its role as an oncoprotein remains to be clarified. In parallel, various nucleosides have been shown to acquire pro-apoptotic properties upon 5'-monophosphorylation in cells. These include triciribine, a tricyclic nucleoside analogue that is currently in clinical trials in combination with a farnesyltransferase inhibitor. Similarly, an N(6)-alkyl-AMP has been shown to be cytotoxic. Interestingly, Rcl has been shown to be inhibited by such compounds in vitro. In order to gain better insight into the precise ligand-recognition determinants, the crystallization of Rcl with these nucleotide analogues was attempted. The first crystal structure of Rcl was solved by molecular replacement using its NMR structure in combination with distantly related crystal structures. The structures of Rcl bound to two other nucleotides were then solved by molecular replacement using the previous crystal structure as a template. The resulting structures, solved at high resolution, led to a clear characterization of the protein-ligand interactions that will guide further rational drug design.

PubMed: 23385460
DOI: 10.1107/S0907444912045039
主引用文献が同じPDBエントリー

実験手法

X-RAY DIFFRACTION (2.44 Å)