5L2R

Crystal structure of fumarate hydratase from Leishmania major

Summary for 5L2R

• Entry DOI: 10.2210/pdb5l2r/pdb
• Descriptor: Fumarate hydratase, (2S)-2-hydroxybutanedioic acid, MALONIC ACID, ... (7 entities in total)
• Functional Keywords: fumarate hydratase fe-s cluster, lyase
• Biological source: Leishmania major
• Total number of polymer chains: 2
• Total formula weight: 135525.68

Authors

Feliciano, P.R.,Drennan, C.L.,Nonato, M.C. (deposition date: 2016-08-02, release date: 2016-08-17, Last modification date: 2023-10-04)

Primary citation

Feliciano, P.R.,Drennan, C.L.,Nonato, M.C.
Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold.
Proc.Natl.Acad.Sci.USA, 113:9804-9809, 2016

PubMed 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.

PubMed: 27528683
DOI: 10.1073/pnas.1605031113

Experimental method

X-RAY DIFFRACTION (2.054 Å)