title: Homology model of the quinohaemoprotein alcohol dehydrogenase from Comamonas testosteroni.
abstract: A molecular model of QH-ADH, the quinohaemoprotein alcohol dehydrogenase from Comamonas testosteroni, has been built by homology modelling. Sequence similarity of N-terminal residues 1-570 with the alpha-subunit of quinoprotein methanol dehydrogenases (MDHs) from Methylophilus methylotrophus W3A1 and Methylobacterium extorquens provided a basis for the design of the PQQ-binding domain of QH-ADH. Minimal sequence similarity with cytochrome c551 from Ectothiorhodospira halophila and cytochrome c5 from Azotobacter vinelandii has been used to model the C-terminal haem c-binding domain, residues 571-677, absent in MDHs. Distance constraints inferred from 19F-NMR relaxation studies of trifluoromethylphenylhydrazine-derivatized PQQ bound to QH-ADH apoenzyme as well as theoretical relations for optimal electron transfer have been employed to position the haem- and PQQ-binding domains relative to each other. The homology model obtained shows overall topological similarity with the crystal structure of cd1-nitrite reductase from Thiosphera pantotropha. The proposed model accounts for the following: (i) the site that is sensitive to in vivo proteolytic attack; (ii) the substrate specificity in comparison with MDHs; (iii) changes of the spectral properties of the haem c upon reconstitution of apo-enzyme with PQQ; (iv) electronic interaction between haem and PQQ; and (v) enantioselectivity in the conversion of a chiral sec alcohol.
authors.affiliation: Kluyver Laboratory for Biotechnology, Delft University of Technology, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Jongejan
authors.forename: J A
authors.initials: JA
authors.lastname: Jongejan
authors.forename: J A
authors.initials: JA
authors.lastname: Duine
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D016946:Gram-Negative Aerobic Rods and Cocci / Q000737:chemistry* / Q000201:enzymology*; D006418:Heme / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015363:Quinolones; D015203:Reproducibility of Results; D017386:Sequence Homology, Amino Acid; D012984:Software
chemical_list: D006420:Hemeproteins; D015363:Quinolones; D006418:Heme; D000426:Alcohol Dehydrogenase