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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.)

Fumarate hydratase isoforms of Leishmania major: Subcellular localization, structural and kinetic properties

Full text
Author(s):
Feliciano, Patricia R. [1] ; Gupta, Shreedhara [2] ; Dyszy, Fabio [3] ; Dias-Baruffi, Marcelo [4] ; Costa-Filho, Antonio J. [5] ; Michels, Paul A. M. [2] ; Nonato, M. Cristina [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, FCFRP, Lab Cristalog Prot, BR-14040903 Ribeirao Preto - Brazil
[2] Catholic Univ Louvain, Duve Inst & Lab Biochem, Trop Dis Res Unit, B-1200 Brussels - Belgium
[3] Univ Sao Paulo, IFSC, Grp Biofis Mol Sergio Mascarenhas, BR-13560970 Sao Carlos, SP - Brazil
[4] Univ Sao Paulo, FCFRP, Lab Glicoimunobiol, BR-14040903 Ribeirao Preto - Brazil
[5] Univ Sao Paulo, FFCLRP, Dept Fis, Lab Biofis Mol, BR-14040901 Ribeirao Preto - Brazil
Total Affiliations: 5
Document type: Journal article
Source: International Journal of Biological Macromolecules; v. 51, n. 1-2, p. 25-31, JUL-AUG 2012.
Web of Science Citations: 14
Abstract

Fumarate hydratases (FHs; EC 4.2.1.2) are enzymes that catalyze the reversible hydration of fumarate to S-malate. Parasitic protists that belong to the genus Leishmania and are responsible for a complex of vector-borne diseases named leishmaniases possess two genes that encode distinct putative FH enzymes. Genome sequence analysis of Leishmania major Friedlin reveals the existence of genes LmjF24.0320 and LmjF29.1960 encoding the putative enzymes LmFH-1 and LmFH-2, respectively. In the present work, the FH activity of both L. major enzymes has been confirmed. Circular dichroism studies suggest important differences in terms of secondary structure content when comparing LmFH isoforms and even larger differences when comparing them to the homologous human enzyme. CD melting experiments revealed that both LmFH isoforms are thermolabile enzymes. The catalytic efficiency under aerobic and anaerobic environments suggests that they are both highly sensitive to oxidation and damaged by oxygen. Intracellular localization studies located LmFH-1 in the mitochondrion, whereas LmFH-2 was found predominantly in the cytosol with possibly also some in glycosomes. The high degree of sequence conservation in different Leishmania species, together with the relevance of FH activity for the energy metabolism in these parasites suggest that FHs might be exploited as targets for broad-spectrum antileishmanial drugs. (c) 2012 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 08/08262-6 - Kinetic, Structural and functional characterization of LmjF24.0320. e LmjF29.1960 genes that code for fumarate hydratase in Leishmania major
Grantee:Maria Cristina Nonato
Support Opportunities: Regular Research Grants
FAPESP's process: 06/05538-5 - Cloning, heterologous expression and characterization of the gene LmjF24.0320 that encodes the enzyme fumarate hydratase in Leishmania major
Grantee:Patrícia Rosa Feliciano
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 09/10454-3 - Studies of the correlation between structure and function of the enzyme fumarate hydratase in Leishmania major
Grantee:Patrícia Rosa Feliciano
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 09/15810-2 - Site-directed spin labeling and Electron Magnetic Resonance: A new approach in studies of lipid-protein and protein-protein interactions
Grantee:Fábio Henrique Dyszy
Support Opportunities: Scholarships in Brazil - Post-Doctoral