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Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling
Laura Masgrau,1,2*Anna Roujeinikova,1,3Linus O. Johannissen,1,2Parvinder Hothi,1,3Jaswir Basran,4Kara E. Ranaghan,5Adrian J. Mulholland,5Michael J. Sutcliffe,1,2Nigel S. Scrutton,1,3David Leys1,3
We present an atomic-level description of the reaction chemistryof an enzyme-catalyzed reaction dominated by proton tunneling.By solving structures of reaction intermediates at near-atomicresolution, we have identified the reaction pathway for tryptamineoxidation by aromatic amine dehydrogenase. Combining experimentand computer simulation, we show proton transfer occurs predominantlyto oxygen O2 of Asp128ß in a reaction dominated bytunneling over 0.6 angstroms. The role of long-range coupledmotions in promoting tunneling is controversial. We show that,in this enzyme system, tunneling is promoted by a short-rangemotion modulating proton-acceptor distance and no long-rangecoupled motion is required.
1 Manchester Interdisciplinary Biocentre, University of Manchester, Jackson's Mill, Post Office Box 88, Manchester M60 1QD, UK. 2 School of Chemical Engineering and Analytical Science, University of Manchester, Jackson's Mill, Post Office Box 88, Manchester M60 1QD, UK. 3 Faculty of Life Sciences, University of Manchester, Jackson's Mill, Post Office Box 88, Manchester M60 1QD, UK. 4 Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK. 5 School of Chemistry, University of Bristol, Cantocks Close, Bristol BS8 1TS, UK.
* Present address: Unité de Bioinformatique Structurale,Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris, France.
To whom correspondence should be addressed. E-mail: david.leys{at}manchester.ac.uk (D.L.); michael.sutcliffe{at}manchester.ac.uk (M.J.S.); adrian.mulholland{at}bristol.ac.uk (A.J.M.); nigel.scrutton{at}manchester.ac.uk (N.S.S.)
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0.6 angstroms. The role of long-range coupled motions in promoting tunneling is controversial. We show that, in this enzyme system, tunneling is promoted by a short-range motion modulating proton-acceptor distance and no long-range coupled motion is required. 
To whom correspondence should be addressed. E-mail: 
