1agn
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X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE
OverviewOverview
The structural determinants of substrate recognition in the human class, IV, or sigmasigma, alcohol dehydrogenase (ADH) isoenzyme were examined, through x-ray crystallography and site-directed mutagenesis. The crystal, structure of sigmasigma ADH complexed with NAD+ and acetate was solved to, 3-A resolution. The human beta1beta1 and sigmasigma ADH isoenzymes share, 69% sequence identity and exhibit dramatically different kinetic, properties. Differences in the amino acids at positions 57, 116, 141, 309, and 317 create a different topology within the sigmasigma, substrate-binding pocket, relative to the beta1beta1 isoenzyme. The, nicotinamide ring of the NAD(H) molecule, in the sigmasigma structure, appears to be twisted relative to its position in the beta1beta1, isoenzyme. In conjunction with movements of Thr-48 and Phe-93, this twist, widens the substrate pocket in the vicinity of the catalytic zinc and may, contribute to this isoenzyme's high Km for small substrates. The presence, of Met-57, Met-141, and Phe-309 narrow the middle region of the sigmasigma, substrate pocket and may explain the substantially decreased Km values, with increased chain length of substrates in sigmasigma ADH. The kinetic, properties of a mutant sigmasigma enzyme (sigma309L317A) suggest that, widening the middle region of the substrate pocket increases Km by, weakening the interactions between the enzyme and smaller substrates while, not affecting the binding of longer alcohols, such as hexanol and retinol.
About this StructureAbout this Structure
1AGN is a Single protein structure of sequence from Homo sapiens with ZN, ACT and NAD as ligands. The following page contains interesting information on the relation of 1AGN with [Alcohol Dehydrogenase]. Active as Alcohol dehydrogenase, with EC number 1.1.1.1 Known structural/functional Sites: , , , , , , and . Full crystallographic information is available from OCA.
ReferenceReference
X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity., Xie P, Parsons SH, Speckhard DC, Bosron WF, Hurley TD, J Biol Chem. 1997 Jul 25;272(30):18558-63. PMID:9228021
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