Homology model of the quinohaemoprotein alcohol dehydrogenase from Comamonas testosteroni

Protein Eng. 1998 Mar;11(3):185-98. doi: 10.1093/protein/11.3.185.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / chemistry*
  • Amino Acid Sequence
  • Binding Sites
  • Gram-Negative Aerobic Rods and Cocci / chemistry*
  • Gram-Negative Aerobic Rods and Cocci / enzymology*
  • Heme / chemistry
  • Hemeproteins / chemistry*
  • Models, Chemical
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Quinolones
  • Reproducibility of Results
  • Sequence Homology, Amino Acid
  • Software


  • Hemeproteins
  • Quinolones
  • Heme
  • Alcohol Dehydrogenase