1tcp
From Proteopedia
|
NMR STRUCTURE DETERMINATION OF TICK ANTICOAGULANT PEPTIDE (TAP)
Overview
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.
About this Structure
1TCP is a Single protein structure of sequence from Ornithodoros moubata. Full crystallographic information is available from OCA.
Reference
NMR structure determination of tick anticoagulant peptide (TAP)., Lim-Wilby MS, Hallenga K, de Maeyer M, Lasters I, Vlasuk GP, Brunck TK, Protein Sci. 1995 Feb;4(2):178-86. PMID:7538849
Page seeded by OCA on Wed Nov 21 03:09:32 2007
