Home News About DMDM Database Statistics Research Publications Contact  

 
Click for a Larger Image
  Domain Name: liver_alcohol_DH_lik
Liver alcohol dehydrogenase. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. There are 7 vertebrate ADH 7 classes, 6 of which have been identified in humans. Class III, glutathione-dependent formaldehyde dehydrogenase, has been identified as the primordial form and exists in diverse species, including plants, micro-organisms, vertebrates, and invertebrates. Class I, typified by liver dehydrogenase, is an evolving form. Gene duplication and functional specialization of ADH into ADH classes and subclasses created numerous forms in vertebrates. For example, the A, B and C (formerly alpha, beta, gamma) human class I subunits have high overall structural similarity, but differ in the substrate binding pocket and therefore in substrate specificity. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine (His-51), the ribose of NAD, a serine (Ser-48) , then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of an beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 20
Total Disease Mutations Found: 4
This domain occurred 13 times on human genes (19 proteins).



  ALCOHOL DEPENDENCE, PROTECTION AGAINST
  PARKINSON DISEASE, SUSCEPTIBILITY TO


Tips:
 If you've navigated here from a protein, hovering over a position on the weblogo will display the corresponding protein position for that domain position.

 The histograms below the weblogo indicate mutations found on the domain. Red is for disease (OMIM) and blue is for SNPs.

 Functional Features are displayed as orange boxes under the histograms. You can choose which features are displayed in the box below.



Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  


Feature Name:Total Found:
NAD binding site
substrate binding site
dimer interface
catalytic Zn binding site
structural Zn binding sit


















Weblogos are Copyright (c) 2002 Regents of the University of California




Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

   |   1000 Hilltop Circle, Baltimore, MD 21250   |   Department of Biological Sciences   |   Phone: 410-455-2258