Premium
NMR solution structure of the recombinant tick anticoagulant protein (rTAP), a factor Xa inhibitor from the tick Ornithodoros moubata
Author(s) -
Antuch W.,
Güntert P.,
Billeter M.,
Hawthorne T.,
Grossenbacher H.,
Wüthrich K.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00941-4
Subject(s) - antiparallel (mathematics) , recombinant dna , chemistry , kunitz sti protease inhibitor , protein secondary structure , beta sheet , tick , protease , protein structure , biology , biochemistry , microbiology and biotechnology , stereochemistry , virology , enzyme , physics , quantum mechanics , magnetic field , gene
The solution structure of the recombinant tick anticoagulant protein (rTAP) was determined by 1 H nuclear magnetic resonance (NMR) spectroscopy in aqueous solution at pH 3.6 and 36°C. rTAP is a 60‐residue protein functioning as a highly specific inhibitor of the coagulation protease factor Xa, which was originally isolated from the tick Ornithodoros moubata . Its regular secondary structure consists of a two‐stranded antiparallel β‐sheet with residues 22–28 and 32–38, and an α‐helix with residues 51–60. The relative orientation of these regular secondary structure elements has nearly identical counterparts in the bovine pancreatic trypsin inhibitor (BPTI). In contrast, the loop between the β‐sheet and the C‐terminal α‐helix as well as the N‐terminal 20‐residue segment preceding the β‐sheet adopt different three‐dimensional folds in the two proteins. These observations are discussed with regard to the implication of different mechanisms of protease inhibition by rTAP and by Kunitz‐type protein proteinase inhibitors.