New insights into the multi-step reaction pathway of the reductive half-reaction catalysed by aromatic amine dehydrogenase: a QM/MM study

2010 ◽  
Vol 46 (18) ◽  
pp. 3104 ◽  
Author(s):  
Jiayun Pang ◽  
Nigel S. Scrutton ◽  
Sam P. de Visser ◽  
Michael J. Sutcliffe
Keyword(s):  
Aromatic Amine ◽  
Reaction Pathway ◽  
Amine Dehydrogenase

scholarly journals The enzyme aromatic amine dehydrogenase induces a substrate conformation crucial for promoting vibration that significantly reduces the effective potential energy barrier to proton transfer

2008 ◽  
Vol 5 (suppl_3) ◽  
pp. 225-232 ◽  
Author(s):  
Linus O Johannissen ◽  
Nigel S Scrutton ◽  
Michael J Sutcliffe
Keyword(s):  
Potential Energy ◽  
Proton Transfer ◽  
Aromatic Amine ◽  
Effective Potential ◽  
Energy Barrier ◽  
Transfer Event ◽  
Effective Potential Energy ◽  
Potential Energy Barrier ◽  
Mechanical Methods ◽  
Amine Dehydrogenase

The role of promoting vibrations in enzymic reactions involving hydrogen tunnelling is contentious. While models incorporating such promoting vibrations have successfully reproduced and explained experimental observations, it has also been argued that such vibrations are not part of the catalytic effect. In this study, we have employed combined quantum mechanical/molecular mechanical methods with molecular dynamics and potential energy surface calculations to investigate how enzyme and substrate motion affects the energy barrier to proton transfer for the rate-limiting H-transfer step in aromatic amine dehydrogenase (AADH) with tryptamine as substrate. In particular, the conformation of the iminoquinone adduct induced by AADH was found to be essential for a promoting vibration identified previously—this lowers significantly the ‘effective’ potential energy barrier, that is the barrier which remains to be surmounted following collective, thermally equilibrated motion attaining a quantum degenerate state of reactants and products. When the substrate adopts a conformation similar to that in the free iminoquinone, this barrier was found to increase markedly. This is consistent with AADH facilitating the H-transfer event by holding the substrate in a conformation that induces a promoting vibration.

Isotope Effects Reveal ThatPara-Substituted Benzylamines Are Poor Reactivity Probes of the Quinoprotein Mechanism for Aromatic Amine Dehydrogenase†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (32) ◽  
pp. 9250-9259 ◽  
Author(s):  
Parvinder Hothi ◽  
Anna Roujeinikova ◽  
Khalid Abu Khadra ◽  
Michael Lee ◽  
Paul Cullis ◽  
...  
Keyword(s):  
Aromatic Amine ◽  
Isotope Effects ◽  
Amine Dehydrogenase

Crystallization and properties of aromatic amine dehydrogenase from Pseudomonas sp

1983 ◽  
Vol 220 (1) ◽  
pp. 253-262 ◽  
Author(s):  
Masayoshi Iwaki ◽  
Toshiharu Yagi ◽  
Kihachiro Horiike ◽  
Yukikazu Saeki ◽  
Tsutomu Ushijima ◽  
...  
Keyword(s):  
Aromatic Amine ◽  
Pseudomonas Sp ◽  
Amine Dehydrogenase

scholarly journals Localization of Periplasmic Redox Proteins ofAlcaligenes faecalis by a Modified General Method for Fractionating Gram-Negative Bacteria

1999 ◽  
Vol 181 (20) ◽  
pp. 6540-6542 ◽  
Author(s):  
Zhenyu Zhu ◽  
Dapeng Sun ◽  
Victor L. Davidson
Keyword(s):  
Aromatic Amine ◽  
Osmotic Shock ◽  
Alcaligenes Faecalis ◽  
Gram Negative Bacteria ◽  
Methylamine Dehydrogenase ◽  
Gram Negative ◽  
Redox Proteins ◽  
Amine Dehydrogenase ◽  
Dependent Growth ◽  
General Method

ABSTRACT A lysozyme-osmotic shock method is described for fractionation ofAlcaligenes faecalis which uses glucose to adjust osmotic strength and multiple osmotic shocks. During phenylethylamine-dependent growth, aromatic amine dehydrogenase, azurin, and a single cytochromec were localized in the periplasm. Their induction patterns are different from those for the related quinoprotein methylamine dehydrogenase and its associated redox proteins.

scholarly journals Ab Initio QM/MM Modeling of the Rate-Limiting Proton Transfer Step in the Deamination of Tryptamine by Aromatic Amine Dehydrogenase

2017 ◽  
Vol 121 (42) ◽  
pp. 9785-9798 ◽  
Author(s):  
Kara E. Ranaghan ◽  
William G. Morris ◽  
Laura Masgrau ◽  
Kittusamy Senthilkumar ◽  
Linus O. Johannissen ◽  
...  
Keyword(s):  
Proton Transfer ◽  
Ab Initio ◽  
Aromatic Amine ◽  
Transfer Step ◽  
Amine Dehydrogenase ◽  
Rate Limiting

scholarly journals Kinetic and chemical mechanisms for the effects of univalent cations on the spectral properties of aromatic amine dehydrogenase

1998 ◽  
Vol 329 (1) ◽  
pp. 175-182 ◽  
Author(s):  
Zhenyu ZHU ◽  
L. Victor DAVIDSON
Keyword(s):  
Absorption Spectrum ◽  
Reaction Mechanism ◽  
Aromatic Amine ◽  
Ph Dependence ◽  
Spectral Change ◽  
Univalent Cations ◽  
Prosthetic Group ◽  
Cation Concentration ◽  
Amine Dehydrogenase ◽  
Spectral Perturbation

Univalent cations and pH influence the UV-visible absorption spectrum of the tryptophan tryptophylquinone (TTQ) enzyme, aromatic amine dehydrogenase (AADH). Little spectral perturbation was observed when pH was varied in the absence of univalent cations. The addition of alkali metal univalent cations (K+, Na+, Li+, Rb+ or Cs+) to oxidized AADH caused significant changes in its absorption spectrum. The apparent Kd for each cation, determined from titrations of the spectral perturbation, decreased with increasing pH. Transient kinetic studies involving rapid mixing of AADH with cations and pH jump revealed that the rate of the cation-induced spectral changes initially decreased with increasing cation concentration to a minimum value, then increased with increasing cation concentration. A kinetic model was developed to fit these data, determine the true pH-independent Kd values for K+ and Na+, and explain the pH-dependence of the apparent Kd. A chemical reaction mechanism, based on the kinetic data, is presented in which the metallic univalent cation facilitates the chemical modification of the TTQ prosthetic group to form an hydroxide adduct which gives rise to the spectral change. Addition of NH4+/NH3 to AADH caused changes in the absorption spectrum which were very different form those caused by addition of the metallic univalent cations. The kinetics of the reaction induced by addition of NH4+/NH3 were also different, being simple saturation kinetics. Another reaction mechanism is proposed for the NH4+/NH3-induced spectral change that involves nucleophilic addition of the unprotonated NH3 to TTQ. The general relevance of these data and models to the physiological reactions of TTQ-dependent enzymes and to the roles of univalent cations in modulating enzyme activity are discussed.

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