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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 studies of the Trypanosoma cruzi Old Yellow Enzyme: Insights into enzyme dynamics and specificity

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Author(s):
Murakami, Mario T. [1] ; Rodrigues, Nathalia C. [2] ; Gava, Lisandra M. [3] ; Honorato, Rodrigo V. [1] ; Canduri, Fernanda [4] ; Barbosa, Leandro R. S. [5] ; Oliva, Glaucius [2] ; Borges, Julio C. [4]
Total Authors: 8
Affiliation:
[1] Lab Nacl Biociencias LNBio CNPEM ABTLuS, BR-13083970 Campinas, SP - Brazil
[2] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil
[3] Univ Fed Sao Carlos, Dept Genet & Evolucao, BR-13565905 Sao Carlos, SP - Brazil
[4] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil
[5] Univ Sao Paulo, Inst Fis, BR-05508090 Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Biophysical Chemistry; v. 184, p. 44-53, DEC 31 2013.
Web of Science Citations: 4
Abstract

The flavoprotein old yellow enzyme of Trypanosoma cruzi (TcOYE) is an oxidoreductase that uses NAD(P)H as cofactor. This enzyme is clinically relevant due to its role in the action mechanism of some ttypanocidal drugs used in the treatment of Chagas' disease by producing reactive oxygen species. In this work, the recombinant enzyme TcOYE was produced and collectively, X-ray crystallography, small angle X-ray scattering, analytical ultracentrifugation and molecular dynamics provided a detailed description of its structure, specificity and hydrodynamic behavior. The crystallographic structure at 1.27 angstrom showed a classical (alpha/beta)(8) fold with the FMN prosthetic group buried at the positively-charged active-site cleft. In solution, TcOYE behaved as a globular monomer, but it exhibited a molecular envelope larger than that observed in the crystal structure, suggesting intrinsic protein flexibility. Moreover, the binding mode of beta-lapachone, a trypanocidal agent, and other naphthoquinones was investigated by molecular docking and dynamics suggesting that their binding to TcOYE are stabilized mainly by interactions with the isoalloxazine ring from FMN and residues from the active-site pocket. (C) 2013 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 11/23110-0 - Using isothermal titration calorimetry for the determination of thermodynamic properties of protein-ligand and protein-protein interactions
Grantee:Julio Cesar Borges
Support type: Regular Research Grants