Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from
Name
Feliciano-2016-Crystal structure of.pdf
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1.31 MB
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Author(s)
Nonato, M. Cristina
Feliciano, Patricia Rosa
Drennan, Catherine L.
Date Issued
August 2016
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
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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Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1605031113
