Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from
Author(s)Nonato, M. Cristina; Feliciano, Patricia Rosa; Drennan, Catherine L.
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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 Å 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 by malonate, 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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemistry
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
Feliciano, Patricia R.; Drennan, Catherine L. and Nonato, M. Cristina. “Crystal Structure of an Fe-S Cluster-Containing Fumarate Hydratase Enzyme fromLeishmania Majorreveals a Unique Protein Fold.” Proceedings of the National Academy of Sciences 113, no. 35 (August 2016): 9804–9809. © 2016 National Academy of Sciences
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