2G8Q

The crystal structure of RNase A from monoclinic crystals at 100 K

2G8Q の概要

• エントリーDOI: 10.2210/pdb2g8q/pdb
• 関連するPDBエントリー: 1AFU 2g8r
• 分子名称: Ribonuclease pancreatic (2 entities in total)
• 機能のキーワード: hydrolase, ribonuclease, endonuclease
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Secreted: P61823
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27416.65

構造登録者

Leonidas, D.D.,Zographos, S.E.,Oikonomakos, N.G. (登録日: 2006-03-03, 公開日: 2006-08-15, 最終更新日: 2024-10-30)

主引用文献

Leonidas, D.D.,Maiti, T.K.,Samanta, A.,Dasgupta, S.,Pathak, T.,Zographos, S.E.,Oikonomakos, N.G.
The binding of 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine to ribonuclease A in the crystal.
Bioorg.Med.Chem., 14:6055-6064, 2006

PubMed Abstract: The binding of a moderate inhibitor, 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine, to ribonuclease A has been studied by X-ray crystallography at 1.7A resolution. Two inhibitor molecules are bound in the central RNA binding cavity of RNase A exploiting interactions with residues from peripheral binding sites rather than from the active site of the enzyme. The uracyl moiety of the first inhibitor molecule occupies the purine-preferring site of RNase A, while the rest of the molecule projects to the solvent. The second inhibitor molecule binds with the carboxyl group at the pyrimidine recognition site and the uridine moiety exploits interactions with RNase A residues Lys66, His119 and Asp121. Comparative structural analysis of the 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine complex with other RNase A-ligand complexes provides a structural explanation of its potency. The crystal structure of the RNase A-3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine complex provides evidence of a novel ligand-binding pattern in RNase A for 3'-N-aminonucleosides that was not anticipated by modelling studies, while it also suggests ways to improve the efficiency and selectivity of such compounds to develop pharmaceuticals against pathologies associated with RNase A homologues.

PubMed: 16730994
DOI: 10.1016/j.bmc.2006.05.011

実験手法

X-RAY DIFFRACTION (1.5 Å)