1p0c

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1p0c, resolution 2.2Å

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Crystal Structure of the NADP(H)-Dependent Vertebrate Alcohol Dehydrogenase (ADH8)

Overview

The amphibian enzyme ADH8, previously named class IV-like, is the only, known vertebrate alcohol dehydrogenase (ADH) with specificity towards, NADP(H). The three-dimensional structures of ADH8 and of the binary, complex ADH8-NADP(+) have been now determined and refined to resolutions, of 2.2A and 1.8A, respectively. The coenzyme and substrate specificity of, ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent, ADHs, suggest a role in aldehyde reduction probably as a retinal, reductase. The large volume of the substrate-binding pocket can explain, both the high catalytic efficiency of ADH8 with retinoids and the high, K(m) value for ethanol. Preference of NADP(H) appears to be achieved by, the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment, of conserved Lys228, which define a binding pocket for the terminal, phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended, conformation that superimposes well with the NAD(H) molecules found in, NAD(H)-dependent ADH complexes. No additional reshaping of the, dinucleotide-binding site is observed which explains why NAD(H) can also, be used as a cofactor by ADH8. The structural features support the, classification of ADH8 as an independent ADH class.

About this Structure

1P0C is a Single protein structure of sequence from Rana porosa with ZN, PO4 and GOL as ligands. Active as Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 Full crystallographic information is available from OCA.

Reference

Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8)., Rosell A, Valencia E, Pares X, Fita I, Farres J, Ochoa WF, J Mol Biol. 2003 Jun 27;330(1):75-85. PMID:12818203

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