Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase

Matthew P. Blakeley; Federico Ruiz; Raul Cachau; Isabelle Hazemann; Flora Meilleur; Andre Mitschler; Stephan Ginell; Pavel Afonine; Oscar N. Ventura; Alexandra Cousido-Siah; Michael Haertlein; Andrzej Joachimiak; Dean Myles; Alberto Podjarny

doi:10.1073/pnas.0711659105

Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase

Matthew P. Blakeley, Federico Ruiz, Raul Cachau, Isabelle Hazemann, Flora Meilleur, Andre Mitschler, Stephan Ginell, Pavel Afonine, Oscar N. Ventura, Alexandra Cousido-Siah, Michael Haertlein, Andrzej Joachimiak, Dean Myles, Alberto Podjarny

Single Crystal Diffraction

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79 Scopus citations

Abstract

We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 Å, 100K; 0.80 Å, 15K; 1.75 Å, 293K), neutron Laue data (2.2 Å, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.

Original language	English
Pages (from-to)	1844-1848
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	6
DOIs	https://doi.org/10.1073/pnas.0711659105
State	Published - Feb 12 2008

Funding

Funders	Funder number
National Institute of General Medical Sciences	R01GM071939

Keywords

Enzymatic mechanism
Helium cooling
Subatomic resolution crystallography
X-ray plus neutrons joint refinement

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10.1073/pnas.0711659105

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Blakeley, M. P., Ruiz, F., Cachau, R., Hazemann, I., Meilleur, F., Mitschler, A., Ginell, S., Afonine, P., Ventura, O. N., Cousido-Siah, A., Haertlein, M., Joachimiak, A., Myles, D., & Podjarny, A. (2008). Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase. Proceedings of the National Academy of Sciences of the United States of America, 105(6), 1844-1848. https://doi.org/10.1073/pnas.0711659105

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title = "Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase",

abstract = "We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 {\AA}, 100K; 0.80 {\AA}, 15K; 1.75 {\AA}, 293K), neutron Laue data (2.2 {\AA}, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.",

keywords = "Enzymatic mechanism, Helium cooling, Subatomic resolution crystallography, X-ray plus neutrons joint refinement",

author = "Blakeley, {Matthew P.} and Federico Ruiz and Raul Cachau and Isabelle Hazemann and Flora Meilleur and Andre Mitschler and Stephan Ginell and Pavel Afonine and Ventura, {Oscar N.} and Alexandra Cousido-Siah and Michael Haertlein and Andrzej Joachimiak and Dean Myles and Alberto Podjarny",

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day = "12",

doi = "10.1073/pnas.0711659105",

language = "English",

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Blakeley, MP, Ruiz, F, Cachau, R, Hazemann, I, Meilleur, F, Mitschler, A, Ginell, S, Afonine, P, Ventura, ON, Cousido-Siah, A, Haertlein, M, Joachimiak, A, Myles, D & Podjarny, A 2008, 'Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 6, pp. 1844-1848. https://doi.org/10.1073/pnas.0711659105

Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase. / Blakeley, Matthew P.; Ruiz, Federico; Cachau, Raul et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 6, 12.02.2008, p. 1844-1848.

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

TY - JOUR

T1 - Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase

AU - Blakeley, Matthew P.

AU - Ruiz, Federico

AU - Cachau, Raul

AU - Hazemann, Isabelle

AU - Meilleur, Flora

AU - Mitschler, Andre

AU - Ginell, Stephan

AU - Afonine, Pavel

AU - Ventura, Oscar N.

AU - Cousido-Siah, Alexandra

AU - Haertlein, Michael

AU - Joachimiak, Andrzej

AU - Myles, Dean

AU - Podjarny, Alberto

PY - 2008/2/12

Y1 - 2008/2/12

N2 - We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 Å, 100K; 0.80 Å, 15K; 1.75 Å, 293K), neutron Laue data (2.2 Å, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.

AB - We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 Å, 100K; 0.80 Å, 15K; 1.75 Å, 293K), neutron Laue data (2.2 Å, 293K), and quantum mechanical modeling. These complementary techniques unveil the internal organization and mobility of the hydrogen bond network that defines the properties of the catalytic engine, explaining how this promiscuous enzyme overcomes the simultaneous requirements of efficiency and promiscuity offering a general mechanistic view for this class of enzymes.

KW - Enzymatic mechanism

KW - Helium cooling

KW - Subatomic resolution crystallography

KW - X-ray plus neutrons joint refinement

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SN - 0027-8424

VL - 105

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EP - 1848

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 6

ER -

Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase

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