3DJO

Bovine Seminal Ribonuclease uridine 2' phosphate complex

3DJO の概要

• エントリーDOI: 10.2210/pdb3djo/pdb
• 関連するPDBエントリー: 3DJP 3DJQ 3DJV 3DJX
• 分子名称: Seminal ribonuclease, PHOSPHORIC ACID MONO-[2-(2,4-DIOXO-3,4-DIHYDRO-2H-PYRIMIDIN-1-YL)-4-HYDROXY-5-HYDROXYMETHYL-TETRAHYDRO-FURAN-3-YL] ESTER, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: ribonuclease, hydrolase, allosteric enzyme, endonuclease, nuclease, secreted
• 由来する生物種: Bos taurus (Bovine)
• 細胞内の位置: Secreted: P00669
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28031.73

構造登録者

Dossi, K.,Leonidas, D.D.,Zographos, S.E.,Oikonomakos, N.G. (登録日: 2008-06-24, 公開日: 2009-06-30, 最終更新日: 2024-11-13)

主引用文献

Dossi, K.,Tsirkone, V.G.,Hayes, J.M.,Matousek, J.,Pouckova, P.,Soucek, J.,Zadinova, M.,Zographos, S.E.,Leonidas, D.D.
Mapping the ribonucleolytic active site of bovine seminal ribonuclease. The binding of pyrimidinyl phosphonucleotide inhibitors
Eur.J.Med.Chem., 44:4496-4508, 2009

PubMed Abstract: Bovine seminal ribonuclease (BS-RNase) is a 27kDa homodimeric enzyme and a member of the pancreatic RNase A superfamily. It is the only RNase with a quaternary structure and it is a mixture of two dimeric forms. In the most abundant form the active site is formed by the swapping of the N-terminal segments. BS-RNase is a potent antitumor agent with severe side effects such as aspermatogenicity, and immunosuppression. As a first step towards the design of potent inhibitors of this enzyme we mapped its active site through the study of the binding of uridine 2'-phosphate (U2'p), uridine 3'-phosphate (U3'p), uridine 5'-diphosphate (UDP), cytidine 3'-phosphate (C3'p), and cytidine 5-phosphate (C5'p), by kinetics, and X-ray crystallography. These phosphonucleotides are potent inhibitors with C3'p being the most potent with a K(i) value of 22 microM. Absorption, distribution, metabolism, and excretion pharmacokinetic property predictions reveal U2'p, U3'p, and C5'p as the most promising with respect to oral bioavailability. In vivo studies on the aspermatogenic effect have shown that C3'p and C5'p inhibit significantly this biological action of BS-RNase.

PubMed: 19643512
DOI: 10.1016/j.ejmech.2009.06.039

実験手法

X-RAY DIFFRACTION (1.6 Å)