Birrer Sandbox 2: Difference between revisions
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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. The initial scene (<scene name='Birrer_Sandbox_2/Whole_adh_molecule/1'>Alcohol Dehydrogenase Overview</scene>) shows an overview of the molecule, allowing for a general look at the tertiary structure of alcohol dehydrogenase (it is complexed with cl, pyz, nad, and zn). A second scene (<scene name='Birrer_Sandbox_2/Close_look_at_ligand/1'>Closer Look at Ligand within Subunit</scene>) shows a close view of the ligand within each subunit. Acidic (negative) residues are selected as well as the NAD. The purple atom is Pyz 378; the green atom on the left is Cl 601, and Zn 375 is the small gray atom at the top. | 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. The initial scene (<scene name='Birrer_Sandbox_2/Whole_adh_molecule/1'>Alcohol Dehydrogenase Overview</scene>) shows an overview of the molecule, allowing for a general look at the tertiary structure of alcohol dehydrogenase (it is complexed with cl, pyz, nad, and zn). A second scene (<scene name='Birrer_Sandbox_2/Close_look_at_ligand/1'>Closer Look at Ligand within Subunit</scene>) shows a close view of the ligand within each subunit. Acidic (negative) residues are selected as well as the NAD. The purple atom is Pyz 378; the green atom on the left is Cl 601, and Zn 375 is the small gray atom at the top. | ||
As far as structure is concerned, alcohol dehydrogenase exists as a tetramer with a zinc molecule complexed in each of the subunits.<ref>Vallee, Bert. L & Hoch, Frederic L. (1955) ''Proc. Natl. Acad. Sci. U.S.A. 41'',327-338. </ref> 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.<ref>''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></ref> | As far as structure is concerned, alcohol dehydrogenase exists as a tetramer with a zinc molecule complexed in each of the subunits.<ref>Vallee, Bert. L & Hoch, Frederic L. (1955) ''Proc. Natl. Acad. Sci. U.S.A. 41'',327-338. </ref> 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.<ref>''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></ref> | ||
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. A second scene shows the whole molecule of ADH complexed with just Zn and EtOH (<scene name='Birrer_Sandbox_2/Adh_plus_zn_and_ethanol/1'>ADH+ZN,ETOH Whole Structure</scene>). A second scene () 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. <ref>''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> </ref> | 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. A second scene shows the whole molecule of ADH complexed with just Zn and EtOH (<scene name='Birrer_Sandbox_2/Adh_plus_zn_and_ethanol/1'>ADH+ZN,ETOH Whole Structure</scene>). A second scene (<scene name='Birrer_Sandbox_2/Ligand_and_3_residues/1'>Ligand + 3 Residues</scene>) 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. <ref>''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> </ref> | ||
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Revision as of 05:54, 24 March 2010
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. The initial scene () shows an overview of the molecule, allowing for a general look at the tertiary structure of alcohol dehydrogenase (it is complexed with cl, pyz, nad, and zn). A second scene () shows a close view of the ligand within each subunit. Acidic (negative) residues are selected as well as the NAD. The purple atom is Pyz 378; the green atom on the left is Cl 601, and Zn 375 is the small gray atom at the top.
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. A second scene shows the whole molecule of ADH complexed with just Zn and EtOH (). A second scene () 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]
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.
Mechanism:
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.