1TQ9

Non-covalent swapped dimer of Bovine Seminal Ribonuclease in complex with 2'-DEOXYCYTIDINE-2'-DEOXYADENOSINE-3',5'-MONOPHOSPHATE

Summary for 1TQ9

• Entry DOI: 10.2210/pdb1tq9/pdb
• Related: 11BA 11BG 1BSR 1N1X 1N3Z 1R3M 1R5C 1R5D
• Descriptor: Ribonuclease, seminal, 2'-DEOXYCYTIDINE-2'-DEOXYADENOSINE-3',5'-MONOPHOSPHATE (3 entities in total)
• Functional Keywords: protein-dinucleotide complex, cytotoxic action, hydrolase
• Biological source: Bos taurus (cattle)
• Cellular location: Secreted: P00669
• Total number of polymer chains: 2
• Total formula weight: 28574.33

Authors

Sica, F.,Di Fiore, A.,Merlino, A.,Mazzarella, L. (deposition date: 2004-06-17, release date: 2004-09-14, Last modification date: 2023-10-25)

Primary citation

Sica, F.,Di Fiore, A.,Merlino, A.,Mazzarella, L.
Structure and Stability of the Non-covalent Swapped Dimer of Bovine Seminal Ribonuclease: AN ENZYME TAILORED TO EVADE RIBONUCLEASE PROTEIN INHIBITOR
J.Biol.Chem., 279:36753-36760, 2004

PubMed Abstract: A growing number of pancreatic-type ribonucleases (RNases) present cytotoxic activity against malignant cells. The cytoxicity of these enzymes is related to their resistance to the ribonuclease protein inhibitor (RI). In particular, bovine seminal ribonuclease (BS-RNase) is toxic to tumor cells both in vitro and in vivo. BS-RNase is a covalent dimer with two intersubunit disulfide bridges between Cys(31) of one chain and Cys(32) of the second and vice versa. The native enzyme is an equilibrium mixture of two isomers, MxM and M=M. In the former the two subunits swap their N-terminal helices. The cytotoxic action is a peculiar property of MxM. In the reducing environment of cytosol, M=M dissociates into monomers, which are strongly inhibited by RI, whereas MxM remains as a non-covalent dimer (NCD), which evades RI. We have solved the crystal structure of NCD, carboxyamidomethylated at residues Cys(31) and Cys(32) (NCD-CAM), in a complex with 2'-deoxycitidylyl(3'-5')-2'-deoxyadenosine. The molecule reveals a quaternary structural organization much closer to MxM than to other N-terminal-swapped non-covalent dimeric forms of RNases. Model building of the complexes between these non-covalent dimers and RI reveals that NCD-CAM is the only dimer equipped with a quaternary organization capable of interfering seriously with the binding of the inhibitor. Moreover, a detailed comparative structural analysis of the dimers has highlighted the residues, which are mostly important in driving the quaternary structure toward that found in NCD-CAM.

PubMed: 15192098
DOI: 10.1074/jbc.M405655200

Experimental method

X-RAY DIFFRACTION (2 Å)