title: Crystal structure of the alcohol dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus at 1.85 A resolution.
abstract: The crystal structure of a medium-chain NAD(H)-dependent alcohol dehydrogenase (ADH) from an archaeon has been solved by multiwavelength anomalous diffraction, using a selenomethionine-substituted enzyme. The protein (SsADH), extracted from the hyperthermophilic organism Sulfolobus solfataricus, is a homo-tetramer with a crystallographic 222 symmetry. Despite the low level of sequence identity, the overall fold of the monomer is similar to that of the other homologous ADHs of known structure. However, a significant difference is the orientation of the catalytic domain relative to the coenzyme-binding domain that results in a larger interdomain cleft. At the bottom of this cleft, the catalytic zinc ion is coordinated tetrahedrally and lacks the zinc-bound water molecule that is usually found in ADH apoform structures. The fourth coordination position is indeed occupied by a Glu residue, as found in bacterial tetrameric ADHs. Other differences are found in the architecture of the substrate pocket whose entrance is more restricted than in other ADHs. SsADH is the first tetrameric ADH X-ray structure containing a second zinc ion playing a structural role. This latter metal ion shows a peculiar coordination, with a glutamic acid residue replacing one of the four cysteine ligands that are highly conserved throughout the structural zinc-containing dimeric ADHs.
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 6, I-80134 Napoli, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Esposito
authors.forename: Filomena
authors.initials: F
authors.lastname: Sica
authors.forename: Carlo Antonio
authors.initials: CA
authors.lastname: Raia
authors.forename: Antonietta
authors.initials: A
authors.lastname: Giordano
authors.forename: Mosè
authors.initials: M
authors.lastname: Rossi
authors.forename: Lelio
authors.initials: L
authors.lastname: Mazzarella
authors.forename: Adriana
authors.initials: A
authors.lastname: Zagari
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016944:Sulfolobus / Q000201:enzymology* / Q000235:genetics; D015032:Zinc / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D009243:NAD; D000426:Alcohol Dehydrogenase; D015032:Zinc