lmmol · Reviews

Alcohol dehydrogenase N-domain biology: redox versatility across systems

🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 1,316 papers from lmmol's literature graph. Citations link to their source on PubMed.

Key proteins at a glance
ProteinPapers
Alcohol dehydrogenase class-P33
Alcohol dehydrogenase 129
Sorbitol dehydrogenase23
All-trans-retinol dehydrogenase [NAD(+)] ADH1B21
NAD(P)H oxidoreductase RTN4IP1, mitochondrial18
NADPH-dependent quinone oxidoreductase VAT118
All-trans-retinol dehydrogenase [NAD(+)] ADH716
Alcohol dehydrogenase class-314

PF08240 covers the N-terminal catalytic platform of zinc-dependent alcohol dehydrogenases, a family conserved from bacteria to humans [1][2][3]. Across organisms, the same fold supports metabolic housekeeping, redox signaling, and context-specific branching [4][5].

1. Structural and catalytic anchors

The domain is most legible when read in context: substrate preference, cofactor geometry, and allosteric constraints map to evolutionary rewiring rather than isolated single-site effects [6][7][8]. Studies repeatedly show that small shifts in partner interactions can reframe function at scale [9][10].

2. Why the family remains clinically useful

In mammals and microbes, this family remains a translational pivot for vascular redox control, toxicity, and disease-relevant metabolism [4][11][12]. In yeast and bacterial systems, perturbing ADH_N-linked pathways often exposes immediate adaptive rewiring [13][14].

3. Practical reading strategy for lmmol users

The strongest neighbors are papers that couple catalytic biochemistry, structural context, and phenotype. Pure annotation-only mentions add little causal signal; robust evidence chains come from studies pairing ADH_N mutations or pathway perturbation with measured outcomes [5][10].

References

  1. Liu L., Hausladen A., Zeng M., Que L. et al. A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. Nature 2001. PubMed 722×
  2. Eklund H., Nordstroem B., Zeppezauer E., Soederlund G. et al. Three-dimensional structure of horse liver alcohol dehydrogenase at 2.4-A resolution. J. Mol. Biol 1976. PubMed 598×
  3. Bennetzen J.L., Hall B.D. The primary structure of the Saccharomyces cerevisiae gene for alcohol dehydrogenase. J. Biol. Chem 1982. PubMed 456×
  4. Liu L., Yan Y., Zeng M., Zhang J. et al. Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell 2004. PubMed 462×
  5. Dennis E.S., Gerlach W.L., Pryor A.J., Bennetzen J.L. et al. Molecular analysis of the alcohol dehydrogenase (Adh1) gene of maize. Nucleic Acids Res 1984. PubMed 234×
  6. Eklund H., Samama J.-P., Jones T.A. Crystallographic investigations of nicotinamide adenine dinucleotide binding to horse liver alcohol dehydrogenase. Biochemistry 1984. PubMed 209×
  7. Thomson J.M., Gaucher E.A., Burgan M.F., De Kee D.W. et al. Resurrecting ancestral alcohol dehydrogenases from yeast. Nat. Genet 2005. PubMed 219×
  8. Kim S.-J., Kim M.-R., Bedgar D.L., Moinuddin S.G.A. et al. Functional reclassification of the putative cinnamyl alcohol dehydrogenase multigene family in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A 2004. PubMed 189×
  9. Berg I.A., Kockelkorn D., Buckel W., Fuchs G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 2007. PubMed 390×
  10. Sirakova T.D., Thirumala A.K., Dubey V.S., Sprecher H. et al. The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J. Biol. Chem 2001. PubMed 143×
  11. Dewanjee S., Das S., Das A.K., Bhattacharjee N. et al. Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets. Eur. J. Pharmacol 2018. PubMed 201×
  12. Hoepfner D., McNamara C.W., Lim C.S., Studer C. et al. Selective and specific inhibition of the plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin. Cell Host Microbe 2012. PubMed 187×
  13. Dixon D.P., Skipsey M., Grundy N.M., Edwards R. Stress-induced protein S-glutathionylation in Arabidopsis. Plant Physiol 2005. PubMed 218×
  14. Birrell G.W., Brown J.A., Wu H.I., Giaever G. et al. Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents. Proc. Natl. Acad. Sci. U.S.A 2002. PubMed 206×
Explore the 885 proteins in this family and the underlying literature graph interactively on lmmol.