1TCP

NMR STRUCTURE DETERMINATION OF TICK ANTICOAGULANT PEPTIDE (TAP)

Summary for 1TCP

• Entry DOI: 10.2210/pdb1tcp/pdb
• Descriptor: TICK ANTICOAGULANT PEPTIDE (1 entity in total)
• Functional Keywords: factor xa serine protease inhibitor, blood coagulation inhibitor
• Biological source: Ornithodoros moubata
• Total number of polymer chains: 1
• Total formula weight: 6992.61

Authors

Brunck, T.K.,Lim-Wilby, M.S.L. (deposition date: 1994-10-31, release date: 1995-10-31, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

SOLUTION NMR