Sequence analysis of fibrolase, a fibrinolytic metalloproteinase from Agkistrodon contortrix contortrix.
Fibrolase is a small (203 amino acids), nonhemorrhagic, fibrinolytic enzyme from the venom of Agkistrodon contortrix contortrix (southern copperhead). While the chemical and physical properties of the protein have been extensively studied, its overall globular structure is unknown. By comparison with homologous metalloproteinases and snake toxins, the catalytic zinc binding site of fibrolase has been identified, as well as a potential binding site for calcium, which has not been recognized before. The positions of the major secondary structural features are predicted, and found to be similar to other structurally characterized metalloproteinases, while the positions of the three intramolecular disulfide bonds are also postulated. Finally, fibrolase is reported to be nonhemorrhagic and earlier work on hemorrhagic enzymes from snake venoms identified six amino acids which might be responsible for hemorrhagic activity. It is shown here that most of these residues occur in fibrolase, and yet it is nonhemorrhagic in its activity. Altogether, this work demonstrates the utility of sequence analysis methods in the characterization of the structure of venom-derived proteins.
Manning
M C
MC
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003435:Crotalid Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D006470:Hemorrhage; D006863:Hydrogen-Ion Concentration; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*; D000097146:Bothrops jararaca Venom
D003435:Crotalid Venoms; D004220:Disulfides; D008666:Metalloendopeptidases; D010975:Platelet Aggregation Inhibitors; D012910:Snake Venoms; D015032:Zinc; D000097146:Bothrops jararaca Venom; C061088:H(2)-proteinase; C058789:fibrolase; C028220:Crotalus adamanteus proteinase II