Quantum Model of Catalysis Based on a Mobile Proton Revealed by Subatomic X-ray and Neutron Diffraction Studies of h-aldose Reductase

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Proceedings of the National Academy of Sciences

DOI:https://doi.org/10.1073/pnas.0711659105· OSTI ID:931156

Blakeley, M. P. ^[1]; Ruiz, Fredrico ^[2]; Cachau, Raul ^[3]; Hazemann, I. ^[4]; Meilleur, Flora ^[4]; Mitschler, A. ^[5]; Ginell, Stephan ^[6]; Afonine, Pavel ^[7]; Ventura, Oscar ^[8]; Cousido-Siah, Alexandra ^[2]; Haertlein, M. ^[4]; Joachimiak, Andrzej ^[6]; Myles, Dean A A ^[9]; Podjarny, A. ^[5]

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1. European Molecular Biology Laboratory (EMBL), France
2. Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, ULP, INSER
3. SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD
4. Institut Laue-Langevin (ILL)
5. IGBMC
6. Argonne National Laboratory (ANL)
7. Lawrence Berkeley National Laboratory (LBNL)
8. Computational Chemical Physics Group, DETEMA, Facultad de Quimica, UdelaR, C.C.1
9. ORNL

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

• Research Organization: Oak Ridge National Laboratory (ORNL)
• Sponsoring Organization: ORNL LDRD Director's R&D
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 931156
• Journal Information: Proceedings of the National Academy of Sciences, Journal Name: Proceedings of the National Academy of Sciences Journal Issue: 6 Vol. 105; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

08 HYDROGEN
EFFICIENCY
ENZYMES
HYDROGEN
NEUTRON DIFFRACTION
NEUTRONS
OXIDOREDUCTASES
PROTONS
SIMULATION