3DJQ

Bovine Seminal Ribonuclease- Uridine 5' diphosphate complex

Summary for 3DJQ

• Entry DOI: 10.2210/pdb3djq/pdb
• Related: 3DJO 3DJP 3DJV 3DJX
• Descriptor: Seminal ribonuclease, URIDINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: ribonuclease, hydrolase, allosteric enzyme, endonuclease, nuclease, secreted
• Biological source: Bos taurus (Bovine)
• Cellular location: Secreted: P00669
• Total number of polymer chains: 2
• Total formula weight: 28073.60

Authors

Dossi, K.,Leonidas, D.D.,Zographos, S.E.,Oikonomakos, N.G. (deposition date: 2008-06-24, release date: 2009-06-30, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.53 Å)