5old

From Proteopedia

X-ray structure of the adduct formed upon reaction of ribonuclease A with a tetranuclear Pt-thiosemicarbazone compound

PDB ID 5old

Drag the structure with the mouse to rotate

Structural highlights

5old is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.78Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RNAS1_BOVIN Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.^[1]

Publication Abstract from PubMed

The tetranuclear Pt complex (PtL)4 (where L(2-) is the anion derived from para-isopropyl thiosemicarbazone) was first described in A.G. Quiroga et al., J. Med. Chem. 41, 1998, 1399-1408. (PtL)4 manifests antiproliferative properties toward various cancer cell lines being a promising anticancer drug candidate. Yet, details of its reactivity with biomolecules have not been elucidated. To this end, we investigated the reactions of (PtL)4 with a few model proteins, i.e. bovine pancreatic ribonuclease (RNase A), cytochrome c (Cyt c) and hen egg white lysozyme (Lysozyme), through electrospray ionization mass spectrometry and other biophysical methods. A rich reactivity of (PtL)4 with the above-mentioned model proteins is observed, leading to the formation of numerous metallodrug-protein adducts. The tetranuclear complex breaks down and various fragments bind proteins up to high metal/protein ratios; this typically results into very complicated mass spectral patterns. However, some of the main mass peaks could be assigned in the case of the Lysozyme adduct. In addition, crystallographic data were obtained for the (PtL)4/Lysozyme and (PtL)4/RNase A adducts pointing at His side chains as the primary binding sites for monometallic Pt fragments. Notably, a few selected features of the interactions observed in the (PtL)4/protein adducts were reproduced by reacting (PtL)4 with a small molecule, i.e. N-methylimidazole. In conclusion, the present study confirms the prodrug nature of the tetraplatinum complex, clarifies one possible pathway for its activation through cluster disassembly and allows initial identification of adducts formed with a representative protein.

Reactions of a tetranuclear Pt-thiosemicarbazone complex with model proteins.,Marzo T, Navas F, Cirri D, Merlino A, Ferraro G, Messori L, Quiroga AG J Inorg Biochem. 2018 Apr;181:11-17. doi: 10.1016/j.jinorgbio.2018.01.002. Epub, 2018 Jan 10. PMID:29353085^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ delCardayre SB, Ribo M, Yokel EM, Quirk DJ, Rutter WJ, Raines RT. Engineering ribonuclease A: production, purification and characterization of wild-type enzyme and mutants at Gln11. Protein Eng. 1995 Mar;8(3):261-73. PMID:7479688
↑ Marzo T, Navas F, Cirri D, Merlino A, Ferraro G, Messori L, Quiroga AG. Reactions of a tetranuclear Pt-thiosemicarbazone complex with model proteins. J Inorg Biochem. 2018 Apr;181:11-17. doi: 10.1016/j.jinorgbio.2018.01.002. Epub, 2018 Jan 10. PMID:29353085 doi:http://dx.doi.org/10.1016/j.jinorgbio.2018.01.002