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Crystal structure of dehydroquinate synthase from Thermus thermophilus HB8 showing functional importance of the dimeric state
Author(s) -
Sugahara Michihiro,
Nodake Yuichi,
Sugahara Mitsuaki,
Kunishima Naoki
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20281
Subject(s) - thermus thermophilus , atp synthase , state (computer science) , crystal structure , chemistry , crystal (programming language) , crystallography , biochemistry , enzyme , computer science , gene , escherichia coli , programming language , algorithm
. Dehydroquinate synthase (DHQS) is a -nicotinamide adenine dinucleotide (NAD )-dependent metalloenzyme that converts 3-deoxy-D-arabino-heptulosonate-7-phosphate to dehydroquinate in the shikimate pathway of bacteria, microbial eukaryotes, and plants. This enzyme is expected to be one of the targets for novel antifungal and antibacterial drug designs, because the shikimate pathway is absent in mammals, and DHQS is required for pathogenic virulence. DHQS is known to have a multistep mechanism, where a single active site catalyzes 5 sequential reactions involving alcohol oxidation, phosphate elimination, carbonyl reduction, ring opening, and intramolecular aldol condensation. The crystal structure of DHQS from Aspergillus nidulans (AnDHQS) in complex with substrates and metal ions elucidated important residues in the active site and ligand-induced intersubunit orientational changes that provide a potential reaction mechanism. The AnDHQS structures also revealed their dimeric state in crystal form, although its biological significance was not fully discussed. This time, we have solved the crystal structure of DHQS from Thermus thermophilus HB8 (TtDHQS) at 1.8 Å resolution, which is the first crystal structure of this enzyme from thermophilic organisms. We show that TtDHQS is present as a homodimer in crystal form, as well as in solution. In this article, we present the structural comparison between AnDHQS and TtDHQS, providing insight into the biological significance of the dimeric state of this enzyme.