3NOY

Crystal structure of IspG (gcpE)

Summary for 3NOY

• Entry DOI: 10.2210/pdb3noy/pdb
• Related: 3DNF 3KE8
• Descriptor: 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, IRON/SULFUR CLUSTER (3 entities in total)
• Functional Keywords: iron-sulfur protein, non-mevalonate pathway, terpene biosynthesis, isoprenoid biosynthesis, tim-barrel n-domain, ferredoxin c-domain, converts 2c-methyl-d-erythritol 2, 4-cyclodiphosphate (me-2, 4cpp), 1-hydroxy-2-methyl-2-(e)-butenyl 4-diphosphate, cytosol, oxidoreductase
• Biological source: Aquifex aeolicus
• Total number of polymer chains: 4
• Total formula weight: 162565.11

Authors

Groll, M.,Graewert, T.,Bacher, A. (deposition date: 2010-06-26, release date: 2010-11-17, Last modification date: 2023-12-27)

Primary citation

Lee, M.,Grawert, T.,Quitterer, F.,Rohdich, F.,Eppinger, J.,Eisenreich, W.,Bacher, A.,Groll, M.
Biosynthesis of isoprenoids: crystal structure of the [4Fe-4S] cluster protein IspG.
J.Mol.Biol., 404:600-610, 2010

PubMed Abstract: IspG protein serves as the penultimate enzyme of the recently discovered non-mevalonate pathway for the biosynthesis of the universal isoprenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate. The enzyme catalyzes the reductive ring opening of 2C-methyl-D-erythritol 2,4-cyclodiphosphate, which affords 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. The protein was crystallized under anaerobic conditions, and its three-dimensional structure was determined to a resolution of 2.7 Å. Each subunit of the c(2) symmetric homodimer folds into two domains connected by a short linker sequence. The N-terminal domain (N domain) is an eight-stranded β barrel that belongs to the large TIM-barrel superfamily. The C-terminal domain (C domain) consists of a β sheet that is flanked on both sides by helices. One glutamate and three cysteine residues of the C domain coordinate a [4Fe-4S] cluster. Homodimer formation involves an extended contact area (about 1100 Å(2)) between helices 8 and 9 of each respective β barrel. Moreover, each C domain contacts the N domain of the partner subunit, but the interface regions are small (about 430 Å(2)). We propose that the enzyme substrate binds to the positively charged surface area at the C-terminal pole of the β barrel. The C domain carrying the iron-sulfur cluster could then move over to form a closed conformation where the substrate is sandwiched between the N domain and the C domain. This article completes the set of three-dimensional structures of the non-mevalonate pathway enzymes, which are of specific interest as potential targets for tuberculostatic and antimalarial drugs.

PubMed: 20932974
DOI: 10.1016/j.jmb.2010.09.050

Experimental method

X-RAY DIFFRACTION (2.7 Å)