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 (1, 2) , Raul Cachau , Isabelle Hazemann (3) , Flora Meilleur , Andre Mitschler (3) , Stephan Ginell , Pavel V. Afonine , Oscar N Ventura , Alexandra Cousido-Siah (3) , Michael Haertlein , Andrzej Joachimiak , Dean Myles , Alberto D. Podjarny (3)

1 CGM - Centre de génétique moléculaire
2 Departamento de Geodinàmica y Paleontologıà, Facultad de Ciencias Experimentales
3 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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

Domaines: Biologie moléculaire

Matthew P Blakeley, Federico Ruiz, Raul Cachau, Isabelle Hazemann, Flora Meilleur, et al.. 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, 2008, 105 (6), pp.1844-8. ⟨10.1073/pnas.0711659105⟩. ⟨hal-00282604⟩