Interaction of Bothrops jararaca venom metalloproteinases with protein inhibitors. 2014

Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
Laboratório Especial de Toxinologia Aplicada-CeTICS, Instituto Butantan, Av. Vital Brasil 1500, 05503-000 São Paulo, Brazil. Electronic address: amanda.asega@butantan.gov.br.

Snake venom metalloproteinases (SVMPs) play important roles in the local and systemic hemorrhage observed upon envenomation. In a previous study on the structural elements important for the activities of HF3 (highly hemorrhagic, P-III-SVMP), bothropasin (hemorrhagic, P-III-SVMP) and BJ-PI (non-hemorrhagic, P-I-SVMP), from Bothrops jararaca, it was demonstrated that they differ in their proteolysis profile of plasma and extracellular matrix proteins. In this study, we evaluated the ability of proteins DM43 and α2-macroglobulin to interfere with the proteolytic activity of these SVMPs on fibrinogen and collagen VI and with their ability to induce hemorrhage. DM43 inhibited the proteolytic activity of bothropasin and BJ-PI but not that of HF3, and was not cleaved the three proteinases. On the other hand, α2-macroglobulin did not inhibit any of the proteinases and was rather cleaved by them. In agreement with these findings, binding analysis showed interaction of bothropasin and BJ-PI but not HF3 to DM43 while none of the proteinases bound to α2-macroglobulin. Moreover, DM43 promoted partial inhibition of the hemorrhagic activity of bothropasin but not that of HF3. Our results demonstrate that metalloproteinases of B. jararaca venom showing different domain composition, glycosylation level and hemorrhagic potency show variable susceptibilities to protein inhibitors.

UI MeSH Term Description Entries
D008297 Male Males
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D003435 Crotalid Venoms Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized. Bothrops Venom,Crotalidae Venoms,Pit Viper Venoms,Rattlesnake Venoms,Crotactin,Crotalid Venom,Crotalin,Crotaline Snake Venom,Crotalotoxin,Crotamin,Pit Viper Venom,Rattlesnake Venom,Snake Venom, Crotaline,Venom, Bothrops,Venom, Crotalid,Venom, Crotaline Snake,Venom, Pit Viper,Venom, Rattlesnake,Venoms, Crotalid,Venoms, Crotalidae,Venoms, Pit Viper,Venoms, Rattlesnake,Viper Venom, Pit
D005340 Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. Coagulation Factor I,Factor I,Blood Coagulation Factor I,gamma-Fibrinogen,Factor I, Coagulation,gamma Fibrinogen
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006470 Hemorrhage Bleeding or escape of blood from a vessel. Bleeding,Hemorrhages

Related Publications

Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
May 2004, Biochemical and biophysical research communications,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
June 2000, Toxicon : official journal of the International Society on Toxinology,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
April 2002, Mediators of inflammation,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
June 2006, Toxicon : official journal of the International Society on Toxinology,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
October 1948, Prensa medica argentina,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
June 1979, La Clinica terapeutica,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
August 1992, Toxicon : official journal of the International Society on Toxinology,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
May 1990, Thrombosis research,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
May 2014, PLoS neglected tropical diseases,
Amanda F Asega, and Ana K Oliveira, and Milene C Menezes, and Ana Gisele C Neves-Ferreira, and Solange M T Serrano
May 1970, Toxicon : official journal of the International Society on Toxinology,
Copied contents to your clipboard!