title: Structure of the GcpE (IspG)-MEcPP complex from Thermus thermophilus.
abstract: Isoprenoid precursor biosynthesis occurs through the mevalonate or the methylerythritol phosphate (MEP) pathway, used i.e., by humans and by many human pathogens, respectively. In the MEP pathway, 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate (MEcPP) is converted to (E)-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate (HMBPP) by the iron-sulfur cluster enzyme HMBPP synthase (GcpE). The presented X-ray structure of the GcpE-MEcPP complex from Thermus thermophilus at 1.55Å resolution provides valuable information about the catalytic mechanism and for rational inhibitor design. MEcPP binding inside the TIM-barrel funnel induces a 60° rotation of the [4Fe-4S] cluster containing domain onto the TIM-barrel entrance. The apical iron of the [4Fe-4S] cluster ligates with the C3 oxygen atom of MEcPP.
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: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ermler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D004896:Erythritol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; 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; C443879:methyl-D-erythritol 2,4-cyclodiphosphate; D004896:Erythritol