Comparison of three classes of human liver alcohol dehydrogenase

• DOI: 10.1111/j.1432-1033.1990.tb19337.x
• Publication Date: 2005-03-04T04:35:21Z
• Authors: Hans EKLUND; Per MÜLLER‐WILLE; Eduardo HORJALES; Olga FUTER; Barton HOLMQUIST; Bert L. VALLEE; Jan‐Olov HÖÖG; Rudolf KAISER; Hans JÖRNVALL
• Keywords: Emphasis (telecommunications); Human liver

Conformational models of the three characterized classes mammalian liver alcohol dehydrogenase were constructed using computer graphics based on known three-dimensional structure E subunit horse enzyme (class I) and primary structures human classes. This correlates substrate-binding pockets class I subunits (alpha, beta gamma in enzyme) with those II III (pi chi, respectively) for enzymes that differ substrate specificity, inhibition pattern many other properties. The sites exhibit pronounced differences both shape Comparing there are no less than 8 10 replacements, respectively, out 11 residues pocket, while isozyme variants, only 1-3 these positions differ. A single residue, Val294, is conserved throughout. dehydrogenases, different substrate-specificity pockets, resemble patterns families such as pancreatic serine proteases. inner part cleft smaller enzyme, because Ser48 Phe93 replaced by larger residues, Thr Tyr, respectively. In II, pocket about half positions. It rich aromatic four Phe one making site distinctly subunits. III, narrow but outer considerably wider more polar enzymes. addition, Ser (or Thr) Tyr instead His51 may influence proton abstraction/donation at active site.