5l2r
From Proteopedia
Crystal structure of fumarate hydratase from Leishmania major
Structural highlights
FunctionPublication Abstract from PubMedFumarate 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 A 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. Crystal structure of an Fe-S cluster-containing fumarate hydratase enzyme from Leishmania major reveals a unique protein fold.,Feliciano PR, Drennan CL, Nonato MC Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):9804-9. doi:, 10.1073/pnas.1605031113. Epub 2016 Aug 15. PMID:27528683[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|