Three-dimensional structure of horse liver alcohol dehydrogenase at 2.4 Å resolution

摘要: Abstract The crystal structure analysis of horse liver alcohol dehydrogenase has been extended to 2.4 A resolution. From the corresponding electron density map apoenzyme we have determined positions 374 amino acids in polypeptide chain each subunit. coenzyme binding domain subunit comprises residues 176 318. 45% these are helical and 32% central six-stranded pleated sheet structure. orientations helices with respect indicate a possible folding mechanism for this part analogue ADP-ribose binds position orientation very similar lactate dehydrogenase. adenine hydrophobic pocket, adenosine ribose is hydrogen-bonded side Asp223, pyrophosphate positioned by interaction Arg47 nicotinamide 6A away from catalytic zinc atom. mainly built up three distinct antiparallel pleated-sheet regions. Residues within provide ligands atom; Cys46, His67 Cys174. An approximate tetrahedral coordination completed water molecule or hydroxyl ion depending on pH. 95 113 form lobe that second atom This liganded distorted arrangement four sulphur atoms cysteine 97, 100, 103 111. forms one significant cleft enzyme surface suggesting region might constitute centre unknown function. two domains separated crevice contains wide deep pocket. at bottom zinc-bound projecting out into Ser48 which turn His51. pocket all probability site substrate moiety coenzyme, lined almost exclusively chains. Both subunits contribute pockets molecule. only accessible polar groups vicinity Thr178 apart