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

被引：75

作者：

Blakeley, Matthew P. ^{[2
]}

Ruiz, Federico ^{[1
]}

Cachau, Raul ^{[3
]}

Hazemann, Isabelle ^{[1
]}

Meilleur, Flora ^{[4
]}

Mitschler, Andre ^{[1
]}

Ginell, Stephan ^{[5
]}

Afonine, Pavel ^{[6
]}

Ventura, Oscar N. ^{[7
]}

Cousido-Siah, Alexandra ^{[1
]}

Haertlein, Michael ^{[2
]}

Joachimiak, Andrzej ^{[5
]}

Myles, Dean ^{[4
]}

Podjarny, Alberto ^{[1
]}

机构：

[1] Inst Natl Sante & Rech Med, Ctr Natl Rech Sci, Inst Genet & Biol Mol & Cellulaire, ULP, F-67404 Illkirch Graffenstaden, France

[2] Inst Laue Langevin, F-38042 Grenoble, France

[3] SAIC Frederick Inc, Natl Canc Inst, Frederick, MD 21702 USA

[4] Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA

[5] Argonne Natl Lab, Struct Biol Ctr, Argonne, IL 60439 USA

[6] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA

[7] Univ Republica, Fac Quim, Computat Chem Phys Grp, Dept Expt & Teoria Estruct Mat & Aplicac, Montevideo 11800, Uruguay

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 06期

关键词：

enzymatic mechanism; helium cooling; subatomic resolution crystallography; x-ray plus neutrons joint refinement;

D O I：

10.1073/pnas.0711659105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We present results of combined studies of the enzyme human aldose reductase (h-AR, 36 kDa) using single-crystal x-ray data (0.66 angstrom, 100K; 0.80 angstrom, 15K; 1.75 angstrom, 293K), neutron Laue data (2.2 angstrom, 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.

引用

页码：1844 / 1848

页数：5

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