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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structural Findings and Molecular Modeling Approach of a TFPI-Like Inhibitor

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Author(s):
Mesquita Pasqualoto, Kerly Fernanda [1] ; Balan, Andrea [2] ; Barreto, Sandra Alves [1] ; Simons, Simone Michaela [1] ; Chudzinski-Tavassi, Ana Marisa [1]
Total Authors: 5
Affiliation:
[1] Inst Butantan, Lab Bioquim & Biofis, BR-05503900 Sao Paulo - Brazil
[2] Brazilian Natl Lab Biosci, Ctr Struct & Mol Biol, BR-13084971 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: PROTEIN AND PEPTIDE LETTERS; v. 21, n. 5, p. 452-457, MAY 2014.
Web of Science Citations: 6
Abstract

Specific blood coagulation inhibitors from hematophagous organisms, with different structures and novel mechanism of action, have been described and they represent promising agents for the treatment of a variety of human diseases related to coagulation and cancer. In our lab, the salivary glands transcriptome of the adult Amblyomma cajennense tick was previously characterized by expressed sequence tags (EST). A transcript that codes for a tissue factor pathway inhibitor (TFPI)-like protein with unique structure was found, and the recombinant form of this protein was named Amblyomin-X. This protein was able to inhibit the factor Xa amidolytic activity and the activation of factor X by the extrinsic tenase complex (FVIIa/TF). Herein, it was performed functional and structural evaluation of Amblyomin-X. The CD assay and molecular dynamics simulations revealed that Amblyomin-X is structurally stable and the naturally unfolded regions as well as the presence of three disulfide bridges in its Kunitz-type domain seem to sustain its inhibitory activity. Regarding the electrostatic potential mapping on the Kunitz-type region, the pattern of charged residues was not quite the same in comparison to human TFPI-1 and TFPI-2, pointing out there might be distinct functional and structural features, which are going to be experimentally exploited. (AU)