PDBsum entry 1bqy

Hydrolase/hydrolase inhibitor

PDB id: 1bqy

Contents

Protein chains

234 a.a. *

Ligands

0GJ ×2

Waters ×162

* Residue conservation analysis

PDB id:

1bqy

Name:

Hydrolase/hydrolase inhibitor

Title:

Plasminogen activator (tsv-pa) from snake venom

Structure:

Plasminogen activator. Chain: a, b. Synonym: tsv-pa. Engineered: yes

Source:

Viridovipera stejnegeri. Stejneger's pit viper. Organism_taxid: 39682. Organ: venom gland. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Not given

Resolution:

2.50Å R-factor: 0.178 R-free: 0.258

Authors:

M.A.A.Parry,W.Bode

Key ref:

M.A.Parry et al. (1998). The crystal structure of the novel snake venom plasminogen activator TSV-PA: a prototype structure for snake venom serine proteinases. Structure, 6, 1195-1206. PubMed id: 9753698 DOI: 10.1016/S0969-2126(98)00119-1

Date:

20-Aug-98 Release date: 20-Aug-99

Protein chains

Q91516  (VSPPA_TRIST) -  Venom plasminogen activator TSV-PA from Trimeresurus stejnegeri

Seq: 258 a.a.

Struc: 234 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.- - ?????

DOI no: 10.1016/S0969-2126(98)00119-1

Structure 6:1195-1206 (1998)

PubMed id: 9753698

The crystal structure of the novel snake venom plasminogen activator TSV-PA: a prototype structure for snake venom serine proteinases.

M.A.Parry, U.Jacob, R.Huber, A.Wisner, C.Bon, W.Bode.

ABSTRACT

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.

Selected figure(s)

Figure 2.
Figure 2. Stereoview superposition of Ca plots of the catalytic domain of human tPA (blue), porcine glandular kallikrein (yellow) and TSV-PA (red). The view and figure labels are as in Figure 1 (standard orientation). The chloromethylketone inhibitor (green) was added in the same orientation as when bound to TSV-PA. (The figure was prepared with MOLSCRIPT [51] and rendered using RASTER3D [52].)

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1195-1206) copyright 1998.

Figure was selected by an automated process.