Atomic description of an enzyme reaction dominated by proton tunneling

Laura Masgrau; Anna Roujeinikova; Linus O. Johannissen; Parvinder Hothi; Jaswir Basran; Kara E. Ranaghan; Adrian J. Mulholland; Michael J. Sutcliffe; Nigel S. Scrutton; David Leys

doi:10.1126/science.1126002

Atomic description of an enzyme reaction dominated by proton tunneling

Laura Masgrau, Anna Roujeinikova, Linus O. Johannissen, Parvinder Hothi, Jaswir Basran, Kara E. Ranaghan, Adrian J. Mulholland, Michael J. Sutcliffe, Nigel S. Scrutton, David Leys

Research output: Contribution to journal › Article › peer-review

Abstract

We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp128β in a reaction dominated by tunneling over ∼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.

Original language	English
Pages (from-to)	237-241
Number of pages	4
Journal	Science
Volume	312
Issue number	5771
DOIs	https://doi.org/10.1126/science.1126002
Publication status	Published - 14 Apr 2006

Keywords

Alcaligenes faecalis/*enzymology
Aspartic Acid/chemistry
Binding Sites
Catalysis
Chemistry, Physical
Computer Simulation
Crystallography, X-Ray
Kinetics
Models, Chemical
Motion
Oxidation-Reduction
Oxidoreductases Acting on CH-NH Group Donors/*chemistry/*metabolism
Oxygen/chemistry
*Protons
Research Support, Non-U.S. Gov't
Temperature
Thermodynamics
Tryptamines/*metabolism
Water/chemistry

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10.1126/science.1126002

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@article{8003fe95dd414438a4759461f9c4b87b,

title = "Atomic description of an enzyme reaction dominated by proton tunneling",

abstract = "We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp128β in a reaction dominated by tunneling over ∼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.",

keywords = "Alcaligenes faecalis/*enzymology, Aspartic Acid/chemistry, Binding Sites, Catalysis, Chemistry, Physical, Computer Simulation, Crystallography, X-Ray, Kinetics, Models, Chemical, Motion, Oxidation-Reduction, Oxidoreductases Acting on CH-NH Group Donors/*chemistry/*metabolism, Oxygen/chemistry, *Protons, Research Support, Non-U.S. Gov't, Temperature, Thermodynamics, Tryptamines/*metabolism, Water/chemistry",

author = "Laura Masgrau and Anna Roujeinikova and Johannissen, {Linus O.} and Parvinder Hothi and Jaswir Basran and Ranaghan, {Kara E.} and Mulholland, {Adrian J.} and Sutcliffe, {Michael J.} and Scrutton, {Nigel S.} and David Leys",

year = "2006",

month = apr,

day = "14",

doi = "10.1126/science.1126002",

language = "English",

volume = "312",

pages = "237--241",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science (A A A S)",

number = "5771",

}

TY - JOUR

T1 - Atomic description of an enzyme reaction dominated by proton tunneling

AU - Masgrau, Laura

AU - Roujeinikova, Anna

AU - Johannissen, Linus O.

AU - Hothi, Parvinder

AU - Basran, Jaswir

AU - Ranaghan, Kara E.

AU - Mulholland, Adrian J.

AU - Sutcliffe, Michael J.

AU - Scrutton, Nigel S.

AU - Leys, David

PY - 2006/4/14

Y1 - 2006/4/14

N2 - We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp128β in a reaction dominated by tunneling over ∼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.

AB - We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp128β in a reaction dominated by tunneling over ∼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.

KW - Alcaligenes faecalis/enzymology

KW - Aspartic Acid/chemistry

KW - Binding Sites

KW - Catalysis

KW - Chemistry, Physical

KW - Computer Simulation

KW - Crystallography, X-Ray

KW - Kinetics

KW - Models, Chemical

KW - Motion

KW - Oxidation-Reduction

KW - Oxidoreductases Acting on CH-NH Group Donors/chemistry/metabolism

KW - Oxygen/chemistry

KW - Protons

KW - Research Support, Non-U.S. Gov't

KW - Temperature

KW - Thermodynamics

KW - Tryptamines/metabolism

KW - Water/chemistry

U2 - 10.1126/science.1126002

DO - 10.1126/science.1126002

M3 - Article

SN - 0036-8075

VL - 312

SP - 237

EP - 241

JO - Science

JF - Science

IS - 5771

ER -

Atomic description of an enzyme reaction dominated by proton tunneling

Abstract

Keywords

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