title: Structure of the E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate synthase (GcpE) from Thermus thermophilus.
abstract: Isoprenoids are biosynthesized via the mevalonate or the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways the latter being used by most pathogenic bacteria, some parasitic protozoa, plant plastids, but not by animals. We determined the X-ray structure of the homodimeric [4Fe-4S] cluster carrying E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate synthase (GcpE) of Thermus thermophilus which catalyzes the penultimate reaction of the MEP pathway and is therefore an attractive target for drug development. The [4Fe-4S] cluster ligated to three cysteines and one glutamate is encapsulated at the intersubunit interface. The substrate binding site lies in front of an (αβ)(8) barrel. The great [4Fe-4S] cluster-substrate distance implicates large-scale domain rearrangements during the reaction cycle.
authors.affiliation: Institut für Klinische Immunologie und Transfusionsmedizin, Justus-Liebig-Universität Giessen, Giessen, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Rekittke
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nonaka
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Demmer
authors.forename: Eberhard
authors.initials: E
authors.lastname: Warkentin
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ermler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016963:Thermus thermophilus / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D004798:Enzymes; D007506:Iron-Sulfur Proteins; D011994:Recombinant Proteins; C421242:hydroxymethylbutenyl 4-diphosphate synthase