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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 112, No. 9, 2017, pp. 617-625
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Bioline Code: oc17087
Full paper language: English
Document type: Research Article
Document available free of charge
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Memórias do Instituto Oswaldo Cruz, Vol. 112, No. 9, 2017, pp. 617-625
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Structural insights into leishmanolysins encoded on chromosome 10 of Leishmania (Viannia) braziliensis
Sutter, Amanda; Antunes, Deborah; Silva-Almeida, Mariana; Costa, Maurício Garcia de Souza & Caffarena, Ernesto Raul
Abstract
BACKGROUND Leishmanolysins have been described as important parasite virulence factors because of their roles in the
infection of promastigotes and resistance to host’s defenses. Leishmania (Viannia) braziliensis contains several leishmanolysin
genes in its genome, especially in chromosome 10. However, the functional impact of such diversity is not understood, but may
be attributed partially to the lack of structural data for proteins from this parasite.
OBJECTIVES This works aims to compare leishmanolysin sequences from L. (V.) braziliensis and to understand how the diversity
impacts in their structural and dynamic features.
METHODS Leishmanolysin sequences were retrieved from GeneDB. Subsequently, 3D models were built using comparative
modeling methods and their dynamical behavior was studied using molecular dynamic simulations.
FINDINGS We identified three subgroups of leishmanolysins according to sequence variations. These differences directly affect
the electrostatic properties of leishmanolysins and the geometry of their active sites. We identified two levels of structural
heterogeneity that might be related to the ability of promastigotes to interact with a broad range of substrates.
MAIN CONCLUSION Altogether, the structural plasticity of leishmanolysins may constitute an important evolutionary adaptation
rarely explored when considering the virulence of L. (V.) braziliensis parasites.
Keywords
Leishmania spp; Leishmania (Viannia) braziliensis; metalloproteases; leishmanolysins; comparative modeling; molecular dynamics
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