Structure of archaeal glyoxylate reductase from Pyrococcus horikoshii OT3 complexed with nicotinamide adenine dinucleotide phosphate

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 63; no. 3; pp. 357 - 365
• Main Authors: Arai, Ryoichi, Masui, Ryoji, Yoshikawa, Seiko, Terada, Takaho, Kinoshita, Yukiko, Wakamatsu, Taisuke, Uchikubo-Kamo, Tomomi, Akasaka, Ryogo, Kuramitsu, Seiki, Shirouzu, Mikako, Yokoyama, Shigeyuki
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England Blackwell Publishing Ltd 01.03.2007
• Subjects: Alcohol Oxidoreductases - chemistry; Amino Acid Sequence; Archaeal Proteins - chemistry; Binding Sites; Dimerization; glyoxylate reductase; hyperthermophilic archaea; Molecular Sequence Data; NAD(P)-dependent dehydrogenases; NADP - chemistry; NADPH; Protein Conformation; Protein Structure, Tertiary; Pyrococcus horikoshii; Pyrococcus horikoshii - enzymology; Sequence Alignment; thermostability
• ISSN: 1399-0047; 0907-4449; 1399-0047
• DOI: 10.1107/S0907444906055442

Glyoxylate reductase catalyzes the NAD(P)H‐linked reduction of glyoxylate to glycolate. Here, the 1.7 Å crystal structure of glyoxylate reductase from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 complexed with nico­tinamide adenine dinucleotide phosphate [NADP(H)] determined by the single‐wavelength anomalous dispersion (SAD) method is reported. The monomeric structure comprises the two domains typical of NAD(P)‐dependent dehydrogenases: the substrate‐binding domain (SBD) and the nucleotide‐binding domain (NBD). The crystal structure and analytical ultracentrifugation results revealed dimer formation. In the NADP(H)‐binding site, the pyrophosphate moiety and the 2′‐­phosphoadenosine moiety are recognized by the glycine‐rich loop (residues 157–162) and by loop residues 180–182, respectively. Furthermore, the present study revealed that P. horikoshii glyoxylate reductase contains aromatic clusters and has a larger number of ion pairs and a lower percentage of hydrophobic accessible surface area than its mesophilic homologues, suggesting its thermostability mechanism.