6MRQ

Structure of ToPI1 inhibitor from Tityus obscurus scorpion venom in complex with trypsin

Summary for 6MRQ

• Entry DOI: 10.2210/pdb6mrq/pdb
• Descriptor: Cationic trypsin, inhibitor from Tityus obscurus scorpion venom (TopI1), CALCIUM ION, ... (5 entities in total)
• Functional Keywords: inhibitor, complex, scorpion, venom, hydrolase, toxin, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 2
• Total formula weight: 29001.05

Authors

Fernandes, J.C.,Mourao, C.B.F.,Schwartz, E.F.,Barbosa, J.A.R.G. (deposition date: 2018-10-15, release date: 2020-07-01, Last modification date: 2024-10-16)

Primary citation

Mourao, C.B.F.,Brand, G.D.,Fernandes, J.P.C.,Prates, M.V.,Bloch Jr., C.,Barbosa, J.A.R.G.,Freitas, S.M.,Restano-Cassulini, R.,Possani, L.D.,Schwartz, E.F.
Head-to-Tail Cyclization after Interaction with Trypsin: A Scorpion Venom Peptide that Resembles Plant Cyclotides.
J.Med.Chem., 63:9500-9511, 2020

PubMed Abstract: Peptidase inhibitors (PIs) have been broadly studied due to their wide therapeutic potential for human diseases. A potent trypsin inhibitor from scorpion venom was characterized and named ToPI1, with 33 amino acid residues and three disulfide bonds. The X-ray structure of the ToPI1:trypsin complex, in association with the mass spectrometry data, indicate a sequential set of events: the complex formation with the inhibitor Lys in the trypsin S1 pocket, the inhibitor C-terminal residue Ser cleavage, and the cyclization of ToPI1 via a peptide bond between residues Ile and Lys. Kinetic and thermodynamic characterization of the complex was obtained. ToPI1 shares no sequence similarity with other PIs characterized to date and is the first PI with CS-α/β motif described from animal venoms. In its cyclic form, it shares structural similarities with plant cyclotides that also inhibit trypsin. These results bring new insights for studies with venom compounds, PIs, and drug design.

PubMed: 32787139
DOI: 10.1021/acs.jmedchem.0c00686

Experimental method

X-RAY DIFFRACTION (1.288 Å)