1bqy

From Proteopedia

Revision as of 13:51, 5 November 2007

PLASMINOGEN ACTIVATOR (TSV-PA) FROM SNAKE VENOM

Overview

BACKGROUND: Trimeresurus stejnejeri venom plasminogen activator (TSV-PA), is a snake venom serine proteinase that specifically activates, plasminogen. Snake venom serine proteinases form a subfamily of, trypsin-like proteinases that are characterised by a high substrate, specificity and resistance to inhibition. Many of these venom enzymes, specifically interfere with haemostatic mechanisms and display a long, circulating half-life. For these reasons several of them have commercial, applications and are potentially attractive pharmacological tools., RESULTS: The crystal structure of TSV-PA has been determined to 2.5 A, resolution and refined to an R factor of 17.8 (R free, 24.4). The enzyme, showing the overall polypeptide fold of trypsin-like serine proteinases, displays unique structural elements such as the presence of a, phenylalanine at position 193, a C-terminal tail clamped via a disulphide, bridge to the 99-loop, and a structurally conserved Asp97 residue. The, presence of a cis proline at position 218 is in agreement with, evolutionary relationships to glandular kallikrein. CONCLUSIONS: We, postulate that Phe 193 accounts for the high substrate specificity of, TSV-PA and renders it incapable of forming a stable complex with bovine, pancreatic trypsin inhibitor and other extended substrates and inhibitors., Mutational studies previously showed that Asp97 is crucial for the, plasminogenolytic activity of TSV-PA, here we identify the conservation of, Asp97 in both types of mammalian plasminogen activator - tissue-type (tPA), and urokinase-type (uPA). It seems likely that Asp97 of tPA and uPA will, have a similar role in plasminogen recognition. The C-terminal extension, of TSV-PA is conserved among snake venom serine proteinases, although its, function is unknown. The three-dimensional structure presented here is the, first of a snake venom serine proteinase and provides an excellent, template for modelling other homologous family members.

About this Structure

1BQY is a Single protein structure of sequence from Viridovipera stejnegeri. Structure known Active Site: . Full crystallographic information is available from OCA.

Reference

The crystal structure of the novel snake venom plasminogen activator TSV-PA: a prototype structure for snake venom serine proteinases., Parry MA, Jacob U, Huber R, Wisner A, Bon C, Bode W, Structure. 1998 Sep 15;6(9):1195-206. PMID:9753698

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