2ERW

Crystal Structure of Infestin 4, a factor XIIa inhibitor

2ERW の概要

• エントリーDOI: 10.2210/pdb2erw/pdb
• 関連するPDBエントリー: 1TBR
• 分子名称: serine protease inhibitor infestin (2 entities in total)
• 機能のキーワード: kazal type domain, blood clotting, hydrolase inhibitor
• 由来する生物種: Triatoma infestans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6198.13

構造登録者

Campos, I.T.N.,Tanaka, A.S.,Barbosa, J.A.R.G. (登録日: 2005-10-25, 公開日: 2006-10-31, 最終更新日: 2024-11-20)

主引用文献

Campos, I.T.,Souza, T.A.,Torquato, R.J.,De Marco, R.,Tanaka-Azevedo, A.M.,Tanaka, A.S.,Barbosa, J.A.R.G.
The Kazal-type inhibitors infestins 1 and 4 differ in specificity but are similar in three-dimensional structure.
Acta Crystallogr.,Sect.D, 68:695-702, 2012

PubMed Abstract: Blood coagulation is an important process in haemostasis, and disorders of blood coagulation can lead to an increased risk of haemorrhage and thrombosis. Coagulation is highly conserved in mammals and has been comprehensively studied in humans in the investigation of bleeding or thrombotic diseases. Some substances can act as inhibitors of blood coagulation and may affect one or multiple enzymes throughout the process. A specific thrombin inhibitor called infestin has been isolated from the midgut of the haematophagous insect Triatoma infestans. Infestin is a member of the nonclassical Kazal-type serine protease inhibitors and is composed of four domains, all of which have a short central α-helix and a small antiparallel β-sheet. Domains 1 and 4 of infestin (infestins 1 and 4) possess specific inhibitory activities. Infestin 1 inhibits thrombin, while infestin 4 is an inhibitor of factor XIIa, plasmin and factor Xa. Here, the structure determination and structural analysis of infestin 1 complexed with trypsin and of infestin 4 alone are reported. Through molecular modelling and docking, it is suggested that the protein-protein binding site is conserved in the infestin 1-thrombin complex compared with other Kazal-type inhibitors. Infestin 4 is able to bind factor XIIa, and the F9N and N11R mutants selected by phage display were shown to be more selective for factor XIIa in comparison to the wild type.

PubMed: 22683792
DOI: 10.1107/S0907444912009067

実験手法

X-RAY DIFFRACTION (1.4 Å)