1tcp
From Proteopedia
(New page: 200px<br /><applet load="1tcp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tcp" /> '''NMR STRUCTURE DETERMINATION OF TICK ANTICOAG...) |
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'''NMR STRUCTURE DETERMINATION OF TICK ANTICOAGULANT PEPTIDE (TAP)'''<br /> | '''NMR STRUCTURE DETERMINATION OF TICK ANTICOAGULANT PEPTIDE (TAP)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Tick anticoagulant peptide (TAP) is a potent and selective 60-amino acid | + | 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== | ==About this Structure== | ||
| - | 1TCP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ornithodoros_moubata Ornithodoros moubata]. Full crystallographic information is available from [http:// | + | 1TCP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ornithodoros_moubata Ornithodoros moubata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TCP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Ornithodoros moubata]] | [[Category: Ornithodoros moubata]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brunck, T | + | [[Category: Brunck, T K.]] |
| - | [[Category: Lim-Wilby, M | + | [[Category: Lim-Wilby, M S.L.]] |
[[Category: factor xa serine protease inhibitor]] | [[Category: factor xa serine protease inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:12:10 2008'' |
Revision as of 13:12, 21 February 2008
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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
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