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Aromatic Amine Dehydrogenase and Long Distance Proton Transfer

This version was saved 12 years, 5 months ago View current version     Page history
Saved by Yawar Malik
on October 30, 2011 at 3:35:15 pm
 

Introduction:

 

Aromatic Amine Dehyrdrogenase (AADH) is a molecule that catalyzes a reaction which converts and amine group to an aldehyde group on certain aromatic compounds.  This reaction has been tracked my X-ray crystallography to bring to light how this occurs.  It has been found that a proton transfer occurs, despite a large energy barrier for this type of reaction.  This is allowed due to the proton's quantum tunneling.

 

Information about AADH as a molecule:

 

AADH is a protein that catalyzes the breakdown of several amino acids.  AADH's are inducible periplasmic quinoproteins in some Gram-negative bacteria.3  It has a molecular weight of 108,900 amu, over double that of the average protein!  It is isoelectric at pH 5.2, meaning it is slightly acidic. It remains active up to 60 degrees celcius, and it contains a prosthetic Tryptophan Tryptophylquinone (TTQ) group, which is what allows it to react.This TTQ group is covalently bonded to the AADH protein as a cofactor.3

 

Fig 1. Structure of TTQ molecule, "Protein" represents where it is bound to AADH

 

The TTQ group allows AADH to act as an enzyme that catalyzes the an oxidation reaction.  This reaction takes in a primary aromatic amine group, water, and an electron acceptor (Which varies based on the bacteria in question) and gives off an aldehyde group, ammonia and a reduced form of the electron acceptor.2  First, TTQ is reduced by the primary amine group, making the aldehyde, then the electron acceptor reoxidized the TTQ group, allowing the protein to continue catalyzing the reaction.  This allows the one enzyme to continually break down amino acids so that the bacteria can use them as a source of carbon and nitrogen3

 

For a full curved arrow mechanism for this reduction reaction, click here: http://www.jbc.org/content/282/33/23766/F1.expansion.html3

 

Aromatic amine dehydrogenase (AADH) is a TTQ dependent quinoprotein and it catalyzes proton transfer by quantum mechanical tunneling. It oxidatively deaminates aromatic primary amines to form aldehydes. The electrons releases are transferred from AADH to the type I blue copper protein azurin and enter the respiratory chain by c –type cytochrome.4 A recent computation study of proton tunneling in AADH reveals that with tryptamine, the degree of tunneling is calculated to exceed 99.9%.5 There are been studies that show that vibrationally assisted tunneling is the most likely mechanism of bond cleavage for the reaction of AADH with benzylamine.6

 

Other enzymes that use tunneling:

 

AADH isn’t the only biological process that uses quantum tunneling. The coenzyme B12- dependent methylmalonyl-CoA mutase also uses it for proton transfer reactions. It shows a very large kinetic isotope effect which indicates that proceeds by a highly quantal tunneling mechanism.  However B12-depedent isomerases and reductases don't have the same mechanism as AADH. They are believed to operate by radical translocation. The observation of very large hydrogen to deuterium (H/D) KIEs for hydrogen radical transfer in several enzymes raises the possibility that tunneling may be a common strategy for the translocation.7

 

References:

 

1. Govindaraj, Shanthi, Edward Eisenstein, Limei H. Jones, Joann Sanders-Loehr, Andrei Y. Chistoserdov, Victor L. Davidson, and Steven L. Edwards. "Aromatic Amine Dehydrogenase, a Second Tryptophan Tryptophylquinone Enzyme." Journal of Bacteriology 176.10 May (1994): 2922-29. Web. 25 Oct. 2011.

 

2. Iwaki, Masayoshi, Toshiharu Yagi, Kihachiro Horike, Yikikazu Saeki, Tsutomu Ushijima, and Mitsuhiro Nozak. "Crystallization and Properties of Aromatic Amine Dehyrdogenase from Pseudomonas sp." Archives of Biochemistry and Biophysics 220.1 Jan. (1983): 253-62. Web. 25 Oct. 2011.

 

3. Roujeinikova, Anna, Parvinder Hothi, Laura Masgrau, Michael J. Sutcliffe, Nigel S. Scrutton, and David Leys. "New Insights into the Reductive Half-reaction Mechanism of Aromatic Amine Dehydrogenase Revealed by Reaction with Carbinolamine Substrates." The Journals of Biological Chemistry 28217 Aug. (2007): 23766-77. Web. 29 Oct. 2011.

 

4. Roujeinikova Anna, Parvinder Hothi, Laura Masgrau, Michael J. Sutcliffe, Nigel S. Scrutton, and David Leys, Linus O. Johannissen, Jaswir Basran, Kara E. Ranaghan, Adrian J. Mulholland. "Atomic Descriptions of an Enzyme Reaction Dominated by Proton Tunneling."  Science April 2006.

 

5. Roujeinikova Anna, Parvinder Hothi, Laura Masgrau, Michael J. Sutcliffe, Nigel S. Scrutton, and David Leys, Linus O. Johannissen, Jaswir Basran, Kara E. Ranaghan, Adrian J. Mulholland. "Hydrogen tunneling in enzyme-catalysed H-transfer reaction: flavoprotein and quinoprotein systems. Phil. Trans. R. Soc. B Aug. 2006.

 

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