Birrer Sandbox 2
Alcohol Dehydrogenase
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| 1htb, resolution 2.40Å () | |||||||||
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| Ligands: | , , , | ||||||||
| Gene: | HUMAN BETA3 CDNA (Homo sapiens) | ||||||||
| Activity: | Alcohol dehydrogenase, with EC number 1.1.1.1 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Alcohol dehydrogenase (PDB id 1htb), or ADH, is an enzyme that catalyzes the oxidation of primary and secondary alcohols to their corresponding aldehydes and ketones through a mechanism that involves the removal of hydrogen. As far as structure is concerned, alcohol dehydrogenase exists as a tetramer with a zinc molecule complexed in each of the subunits.[1] It has a SCOP catagory of an alpha and beta protein. It does contain at the N-terminal a domain that is all beta; however, the C-Terminal domain is alpha and beta, so the catagory is alpha and beta. The C-Terminal core has 3 layers of alpha/beta/alpha and parallel beta sheets of 6 strands.[2]
In the oxidation mechanism, ADH is momentarily associated with nicontinamide adenine dinucleotide (NAD+), which functions as a cosubstrate. In its reaction, alcohol dehydrogenase uses zinc and NAD to facilitate the reaction. The function of zinc is to position the –OH group on the ethanol in a conformation that allows for the oxidation to occur. NAD then acts as a cosubstrate and performs the oxidation. shows a picture of this interaction, with two ethanol molecules attached to the active sites. In the picture Zinc is positioned between Cys46, Cys174, and His67, all polar side chains. Ethanol, then, binds to the zinc which is next to the NAD cosubstrate. [3] Another view of the structure of alcohol dehydrogenase can be seen through the complex of alcohol dehydrogenase and just NAD and Zn in . 1 final image of the protein can be seen in a complex with NAD, Zn, and this time a phosphate group. shows the structure of this specific complex.
The of alcohol dehydrogenase reaction is as follows: CH3CH2OH + NAD+ -> CH3COH (acetaldehyde) + NADH + H+ (Note: The reaction is actually reversible although the arrow does not show it) [4] The alcohol dehydrogenase reaction is a bisubstrate reaction, where ADH catalyzed the transfer of a hydride ion from ethanol to NAD+. In metabolic reactions within the human liver, glyceraldehyde is reduced to glycerol through a mechanism in which NADH is reduced to NAD+, and this whole process is catalyzed by alcohol dehydrogenase.
ReferencesReferences
- ↑ Vallee, Bert. L & Hoch, Frederic L. (1955) Proc. Natl. Acad. Sci. U.S.A. 41,327-338.
- ↑ Protein: Alcohol dehydrogenase from Human (Homo sapiens), different isozymes. SCOP. 2009. 1 March 2010 < http://scop.berkeley.edu/data/scop.b.d.c.b.b.c.html>
- ↑ Alcohol Dehydrogenase. Protein Data Bank. 2010. RCSB. 1 March 2010 <http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb13_3.html>
- ↑ Voet, et. al. Fundamentals of Biochemistry: 3rd Edition. Hoboken: Wiley & Sons, Inc, 2008.