1RHY

Crystal structure of Imidazole Glycerol Phosphate Dehydratase

Summary for 1RHY

• Entry DOI: 10.2210/pdb1rhy/pdb
• Descriptor: Imidazole glycerol phosphate dehydratase, MERCURY (II) ION, ETHYL MERCURY ION, ... (7 entities in total)
• Functional Keywords: dehydratases; histidine biosynthesis; left-handed b-a-b crossover motif; gene duplication, lyase
• Biological source: Filobasidiella neoformans
• Total number of polymer chains: 2
• Total formula weight: 46881.34

Authors

Sinha, S.C.,Chaudhuri, B.N.,Burgner, J.W.,Yakovleva, G.,Davisson, V.J.,Smith, J.L. (deposition date: 2003-11-14, release date: 2004-05-04, Last modification date: 2024-02-14)

Primary citation

Sinha, S.C.,Chaudhuri, B.N.,Burgner, J.W.,Yakovleva, G.,Davisson, V.J.,Smith, J.L.
Crystal structure of imidazole glycerol-phosphate dehydratase: duplication of an unusual fold
J.Biol.Chem., 279:15491-15498, 2004

PubMed Abstract: Imidazole glycerol-phosphate dehydratase (IGPD) catalyzes the sixth step of histidine biosynthesis. The enzyme is of fundamental biochemical interest, because it catalyzes removal of a non-acidic hydrogen atom in the dehydration reaction. It is also a potential target for development of herbicides. IGPD is a metalloenzyme in which transition metals induce aggregation and are required for catalysis. Addition of 1 equivalent of Mn(2+)/subunit is shown by analytical ultracentrifugation to induce the formation of 24-mers from trimeric IGPD. Two histidine-rich motifs may participate in metal binding and aggregation. The 2.3-A crystal structure of metal-free trimeric IGPD from the fungus Filobasidiella neoformans reveals a novel fold containing an internal repeat, apparently the result of gene duplication. The 95-residue alpha/beta half-domain occurs in a few other proteins, including the GHMP kinase superfamily (galacto-homoserine-mevalonate-phosphomevalonate), but duplication to form a compact domain has not been seen elsewhere. Conserved residues cluster at two types of sites in the trimer, each site containing a conserved histidine-rich motif. A model is proposed for the intact, active 24-mer in which all highly conserved residues, including the histidine-rich motifs in both the N- and C-terminal halves of the polypeptide, cluster at a common site between trimers. This site is a candidate for the active site and also for metal binding leading to aggregation of trimers. The structure provides a basis for further studies of enzyme function and mechanism and for development of more potent and specific herbicides.

PubMed: 14724278
DOI: 10.1074/jbc.M312733200

Experimental method

X-RAY DIFFRACTION (2.3 Å)