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 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.
authors.affiliation: Institut Laue Langevin, 6, Rue Jules Horowitz, BP 156, 38042 Grenoble, France.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Blakeley
authors.forename: Federico
authors.initials: F
authors.lastname: Ruiz
authors.forename: Raul
authors.initials: R
authors.lastname: Cachau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hazemann
authors.forename: Flora
authors.initials: F
authors.lastname: Meilleur
authors.forename: Andre
authors.initials: A
authors.lastname: Mitschler
authors.forename: Stephan
authors.initials: S
authors.lastname: Ginell
authors.forename: Pavel
authors.initials: P
authors.lastname: Afonine
authors.forename: Oscar N
authors.initials: ON
authors.lastname: Ventura
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cousido-Siah
authors.forename: Michael
authors.initials: M
authors.lastname: Haertlein
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.forename: Dean
authors.initials: D
authors.lastname: Myles
authors.forename: Alberto
authors.initials: A
authors.lastname: Podjarny
mesh_terms: D000449:Aldehyde Reductase / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D008958:Models, Molecular; D009502:Neutrons; D011522:Protons; D011789:Quantum Theory; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D011522:Protons; D000449:Aldehyde Reductase