title: Small serum protein-1 changes the susceptibility of an apoptosis-inducing metalloproteinase HV1 to a metalloproteinase inhibitor in habu snake (Trimeresurus flavoviridis).
abstract: Viperidae snakes containing various venomous proteins also have several anti-toxic proteins in their sera. However, the physiological function of serum protein has been elucidated incompletely. Small serum protein (SSP)-1 is a major component of the SSPs isolated from the serum of a Japanese viper, the habu snake (Trimeresurus flavoviridis). It exists in the blood as a binary complex with habu serum factor (HSF), a snake venom metalloproteinase inhibitor. Affinity chromatography of the venom on an SSP-1-immobilized column identified HV1, an apoptosis-inducing metalloproteinase, as the target protein of SSP-1. Biacore measurements revealed that SSP-1 was bound to HV1 with a dissociation constant of 8.2 × 10⁻⁸ M. However, SSP-1 did not inhibit the peptidase activity of HV1. Although HSF alone showed no inhibitory activity or binding affinity to HV1, the SSP-1-HSF binary complex bound to HV1 formed a ternary complex that non-competitively inhibited the peptidase activity of HV1 with a inhibition constant of 5.1 ± 1.3 × 10⁻⁹ M. The SSP-1-HSF complex also effectively suppressed the apoptosis of vascular endothelial cells and caspase 3 activation induced by HV1. Thus, SSP-1 is a unique protein that non-covalently attaches to HV1 and changes its susceptibility to HSF.
authors.affiliation: Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka 814-0180, Japan. anarumi@fukuoka-u.ac.jp
authors.forename: Narumi
authors.initials: N
authors.lastname: Shioi
authors.forename: Eiki
authors.initials: E
authors.lastname: Ogawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mizukami
authors.forename: Shuhei
authors.initials: S
authors.lastname: Abe
authors.forename: Rieko
authors.initials: R
authors.lastname: Hayashi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Terada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D007700:Kinetics; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008958:Models, Molecular; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011480:Protease Inhibitors / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D030162:Reptilian Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity; D017841:Trimeresurus / Q000097:blood / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D003435:Crotalid Venoms; D055767:Immobilized Proteins; D010446:Peptide Fragments; D011480:Protease Inhibitors; D030162:Reptilian Proteins; D045726:Metalloproteases; C505407:CASP3 protein, human; D053148:Caspase 3