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

Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold

Full text
Feliciano, Patricia R. ; Drennan, Catherine L. ; Cristina Nonato, M.
Total Authors: 3
Document type: Journal article
Source: Proceedings of the National Academy of Sciences of the United States of America; v. 113, n. 35, p. 9804-9809, AUG 30 2016.
Web of Science Citations: 6

Fumarate hydratases (FHs) are essential metabolic enzymes grouped into two classes. Here, we present the crystal structure of a class I FH, the cytosolic FH from Leishmania major, which reveals a previously undiscovered protein fold that coordinates a catalytically essential {[}4Fe-4S] cluster. Our 2.05 angstrom resolution data further reveal a dimeric architecture for this FH that resembles a heart, with each lobe comprised of two domains that are arranged around the active site. Besides the active site, where the substrate S-malate is bound bidentate to the unique iron of the {[}4Fe-4S] cluster, other binding pockets are found near the dimeric enzyme interface, some of which are occupied bymalonate, shown here to be a weak inhibitor of this enzyme. Taken together, these data provide a framework both for investigations of the class I FH catalytic mechanism and for drug design aimed at fighting neglected tropical diseases. (AU)

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 type: Scholarships in Brazil - Doctorate
FAPESP's process: 11/19674-6 - Structure determination of fumarate hydratase isoforms from Leishmania major
Grantee:Patrícia Rosa Feliciano
Support type: Scholarships abroad - Research Internship - Doctorate
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 type: Regular Research Grants