Cell. Mol. Life Sci. 65 (2008) 3879 – 3894 View metadata,1420-682X/08/243879-16 citation and similar papers at core.ac.uk Cellular and Molecular Life Sciencesbrought to you by CORE DOI 10.1007/s00018-008-8587-z provided by Springer - Publisher Connector Birkhuser Verlag, Basel, 2008 The MDR superfamily B. Perssona,b,*, J. Hedlunda and H. Jçrnvallc a IFM Bioinformatics, Linkçping University, 581 83 Linkçping (Sweden), Fax: +4613137568, e-mail:
[email protected] b Dept of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm (Sweden) c Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm (Sweden) Online First 14 November 2008 Abstract. The MDR superfamily with ~350-residue ments. Subsequent recognitions now define at least 40 subunits contains the classical liver alcohol dehydro- human MDR members in the Uniprot database genase (ADH), quinone reductase, leukotriene B4 (correspondingACHTUNGRE to 25 genes when excluding close dehydrogenase and many more forms. ADH is a homologues), and in all species at least 10888 entries. dimeric zinc metalloprotein and occurs as five differ- Overall, variability is large, but like for many dehy- ent classes in humans, resulting from gene duplica- drogenases, subdivided into constant and variable tions during vertebrate evolution, the first one traced forms, corresponding to household and emerging to ~500 MYA (million years ago) from an ancestral enzyme activities, respectively. This review covers formaldehyde dehydrogenase line. Like many dupli- basic facts and describes eight large MDR families and cations at that time, it correlates with enzymogenesis nine smaller families. Combined, they have specific of new activities, contributing to conditions for substrates in metabolic pathways, some with wide emergence of vertebrate land life from osseous fish.