ArticleProceedings of the National Academy of Sciences of the United States of America2016
Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Evidence for ecological adaptation of reductive citric acid and reverse oxidative citric acid cycles based on a survey of genomes from autotrophicFEMS microbes · 2026Review
- Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers.Cold Spring Harbor perspectives in medicine · 2024Review
- Introducing CRAFT: The Center for Research and Advancement in Fragments and molecular Targets.ACS medicinal chemistry letters · 2024Article
- Enantioselectivity in the enzymatic dehydration of malate and tartrate: Mirror image specificities of structurally similar dehydratases.Protein science : a publication of the Protein Society · 2023Article
- Chemoproteomics Reveals Disruption of Metal Homeostasis and Metalloproteins by the Antibiotic Holomycin.ACS chemical biology · 2023Article
- Interchangeability of class I and II fumarases in an obligate methanotroph Methylotuvimicrobium alcaliphilum 20Z.PloS one · 2023Article
- Aurothiomalate-Based Drugs as Potentially Novel Agents Against Leishmania major: A Mini Review.Acta parasitologica · 2022Review
- Women in science symposium.Biophysical reviews · 2021Article
- A combination of Class-I fumarases and metabolites (α-ketoglutarate and fumarate) signal the DNA damage response inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural and Biochemical Investigations of the [4Fe-4S] Cluster-Containing Fumarate Hydratase fromBiochemistry · 2019Article
- Crystal Structures of Fumarate Hydratases from Leishmania major in a Complex with Inhibitor 2-Thiomalate.ACS chemical biology · 2019Article
- Biochemical characterization and essentiality ofThe Journal of biological chemistry · 2018Article
- Protein structure determination using metagenome sequence data.Science (New York, N.Y.) · 2017Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
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.
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