3FL0

X-ray structure of the non covalent swapped form of the Q28L/K31C/S32C mutant of bovine pancreatic ribonuclease in complex with 2'-DEOXYCYTIDINE-2'-DEOXYGUANOSINE-3',5'-MONOPHOSPHATE

Summary for 3FL0

• Entry DOI: 10.2210/pdb3fl0/pdb
• Related: 1A2W 1BSR 1H8X 1TQ9 3BCP 3FKZ 3FL1 3FL3
• Descriptor: Ribonuclease pancreatic, 2'-DEOXYCYTIDINE-2'-DEOXYGUANOSINE-3',5'-MONOPHOSPHATE (3 entities in total)
• Functional Keywords: 3d-domain swapping, bovine seminal ribonuclease, non-covalent dimer, antitumor activity, quaternary structure flexibility, protein mutations and evolution, endonuclease, glycation, glycoprotein, hydrolase, nuclease, secreted
• Biological source: Bos taurus (Bovine)
• Cellular location: Secreted: P61823
• Total number of polymer chains: 2
• Total formula weight: 28151.39

Authors

Merlino, A.,Russo Krauss, I.,Perillo, M.,Mattia, C.A.,Ercole, C.,Picone, D.,Vergara, A.,Sica, F. (deposition date: 2008-12-18, release date: 2009-03-24, Last modification date: 2023-11-01)

Primary citation

Merlino, A.,Russo Krauss, I.,Perillo, M.,Mattia, C.A.,Ercole, C.,Picone, D.,Vergara, A.,Sica, F.
Toward an antitumor form of bovine pancreatic ribonuclease: The crystal structure of three noncovalent dimeric mutants
Biopolymers, 91:1029-1037, 2009

PubMed Abstract: The cytotoxic action of bovine seminal ribonuclease (BS-RNase) depends on its noncovalent swapped dimeric form (NCD-BS), which presents a compact structure that allows the molecule to escape ribonuclease inhibitor (RI). A key role in the acquisition of this structure has been attributed to the concomitant presence of a proline in position 19 and a leucine in position 28. The introduction of Leu28, Cys31, and Cys32 and, in addition, of Pro19 in the sequence of bovine pancreatic ribonuclease (RNase A) has produced two dimeric variants LCC and PLCC, which do exhibit a cytotoxic activity, though at a much lower level than BS-RNase. The crystal structure analysis of the noncovalent swapped form (NCD) of LCC and PLCC, complexed with the substrate analogue 2 '-deoxycytidylyl(3 ',5 ')-2 '-deoxyguanosine, has revealed that, differently from NCD-BS, the dimers adopt an opened quaternary structure, with the two Leu residues fully exposed to the solvent, that does not hinder the binding of RI. Similar results have been obtained for a third mutant of the pancreatic enzyme, engineered with the hinge peptide sequence of the seminal enzyme (residues 16-22) and the two cysteines in position 31 and 32, but lacking the hydrophobic Leu residue in position 28. The comparison of these three structures with those previously reported for other ribonuclease swapped dimers strongly suggests that, in addition to Pro19 and Leu28, the presence of a glycine at the N-terminal end of the hinge peptide is also important to push the swapped form of RNase A dimer into the compact quaternary organization observed for NCD-BS.

PubMed: 19280639
DOI: 10.1002/bip.21183

Experimental method

X-RAY DIFFRACTION (1.94 Å)