Molecular basis for the partition of the essential functions of thrombin among snake venom serine proteinases: the case of thrombin-like enzymes.
Thrombin is a mammalian serine proteinase that plays a prominent role in the maintenance and regulation of hemostasis through its interaction with various substrates and/or ligands. The venoms of several snakes contain glycosylated serine proteinases that have been recognized to possess one or more of the essential activities of thrombin on fibrinogen (Fg) and/or platelets. These proteinases share about 60% sequence identity. One class of snake venom serine proteinases are those known as thrombin-like (TLE), named after their ability to directly clot Fg in order to preferentially produce fibrinopeptide A, fibrinopeptide B or both. To understand the molecular basis of this phenomenon, the corresponding amino acid sequences and molecular structures need to be analyzed. Given the absence of experimentally determined tertiary structures of snake venom, TLEs, three-dimensional molecular models should prove useful in this context. Towards this goal, we obtained models of snake venom TLEs that used TSV-PA as template, TSV-PA being the only snake venom serine proteinase whose crystal structure is known to date. Along with a comparative sequence analysis the models contribute to the identification and description of thrombin-homologous or alternative binding sites, helping thus to understand differences in specificity.
Maroun
R C
RC
Venom Unit, Institut Pasteur, 25 rue du Docteur-Roux, F-75724 Paris Cedex 15, France. rmaroun@pasteur.fr
D000595:Amino Acid Sequence; D000818:Animals; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D012910:Snake Venoms / Q000737:chemistry / Q000201:enzymology* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000235:genetics / Q000502:physiology*
D006023:Glycoproteins; D012910:Snake Venoms; D010960:Plasminogen Activators; D012697:Serine Endopeptidases; C093329:TSV-PA protein, Trimeresurus stejnegeri; D013917:Thrombin