1TCP

NMR STRUCTURE DETERMINATION OF TICK ANTICOAGULANT PEPTIDE (TAP)

1TCP の概要

• エントリーDOI: 10.2210/pdb1tcp/pdb
• 分子名称: TICK ANTICOAGULANT PEPTIDE (1 entity in total)
• 機能のキーワード: factor xa serine protease inhibitor, blood coagulation inhibitor
• 由来する生物種: Ornithodoros moubata
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6992.61

構造登録者

Brunck, T.K.,Lim-Wilby, M.S.L. (登録日: 1994-10-31, 公開日: 1995-10-31, 最終更新日: 2024-11-20)

主引用文献

Lim-Wilby, M.S.,Hallenga, K.,de Maeyer, M.,Lasters, I.,Vlasuk, G.P.,Brunck, T.K.
NMR structure determination of tick anticoagulant peptide (TAP).
Protein Sci., 4:178-186, 1995

PubMed Abstract: Tick anticoagulant peptide (TAP) is a potent and selective 60-amino acid inhibitor of the serine protease Factor Xa (fXa), the penultimate enzyme in the blood coagulation cascade. The structural features of TAP responsible for its remarkable specificity for fXa are unknown, but the binding to its target appears to be unique. The elucidation of the TAP structure may facilitate our understanding of this new mode of serine protease inhibition and could provide a basis for the design of novel fXa inhibitors. Analyses of homo- and heteronuclear two-dimensional NMR spectra (total correlation spectroscopy, nuclear Overhauser effect spectroscopy [NOESY], constant time heteronuclear single quantum correlation spectroscopy [CT-HSQC], and HSQC-NOESY; 600 MHz; 1.5 mM TAP; pH 2.5) of unlabeled, 13C-labeled, and 15N-labeled TAP provided nearly complete 1H sequence-specific resonance assignments. Secondary structural elements were identified by characteristic NOE patterns and D2O amide proton-exchange experiments. A three-dimensional structure of TAP was generated from 412 NOESY-derived distance and 47 dihedral angle constraints. The structural elements of TAP are similar in some respects to those of the Kunitz serine protease inhibitor family, with which TAP shares weak sequence homology. This structure, coupled with previous kinetic and biochemical information, confirms previous suggestions that TAP has a unique mode of binding to fXa.

PubMed: 7538849

実験手法

SOLUTION NMR