High-resolution structure of a Kazal-type serine protease inhibitor from the dengue vector Aedes aegypti

High-resolution structure of a Kazal-type serine protease inhibitor from the dengue vector Aedes aegypti

Author Torquato, Ricardo J. S. Autor UNIFESP Google Scholar
Lu, Stephen Autor UNIFESP Google Scholar
Martins, Nadia Helena Google Scholar
Tanaka, Aparecida S. Autor UNIFESP Google Scholar
Barbosa Pereira, Pedro Jose Google Scholar
Abstract Blood-feeding exoparasites are rich sources of protease inhibitors, and the mosquito Aedes aegypti, which is a vector of Dengue virus, Yellow fever virus, Chikungunya virus and Zika virus, is no exception. AaTI is a single-domain, noncanonical Kazal-type serine proteinase inhibitor from A. aegypti that recognizes both digestive trypsin-like serine proteinases and the central protease in blood clotting, thrombin, albeit with an affinity that is three orders of magnitude lower. Here, the 1.4 angstrom resolution crystal structure of AaTI is reported from extremely tightly packed crystals (similar to 22% solvent content), revealing the structural determinants for the observed inhibitory profile of this molecule.
Keywords anticoagulants
thrombin
trypsin
salivary glands
protein-protein interactions
Kazal inhibitor
Aedes aegypti
Dengue fever
Yellow fever
Zika virus
Language English
Sponsor FAPESP
CNPq
Special Visiting Researcher Program (PVE - Bolsa Pesquisador Visitante Especial)
FCT - Fundação para a Ciencia e a Tecnologia in the form of the 'Institute for Research and Innovation in Health Sciences' project
European Regional Development Fund (FEDER) through the COMPETE - Operational Programme for Competitiveness and Internationalization (POCI), PORTUGAL
Structured program on bioengineered therapies for infectious diseases and tissue regeneration
Norte Portugal Regional Operational Programme
FEDER
CNPq
Grant number FAPESP: 12/03657-8
CNPq: 478504/2013-6
CNPq: 400835/2014-2
CNPq: 308780/2013-2
PVE: 400835/2014-2
FCT: POCI-01-0145-FEDER-007274
Structured program on bioengineered therapies for infectious diseases and tissue regeneration: Norte-01-0145-FEDER-000012
NORTE: 2020
Date 2017
Published in Acta Crystallographica Section F-Structural Biology Communications. Chester, v. 73, p. 469-475, 2017.
ISSN 2053-230X (Sherpa/Romeo, impact factor)
Publisher Int Union Crystallography
Extent 469-475
Origin http://dx.doi.org/10.1107/S2053230X17010007
Access rights Closed access
Type Article
Web of Science ID WOS:000406871600005
URI http://repositorio.unifesp.br/handle/11600/51475

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