Quantum model of catalysis based on a mobile proton revealed by subatomic x-ray and neutron diffraction studies of h-aldose reductase.
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.
Blakeley
Matthew P
MP
Institut Laue Langevin, 6, Rue Jules Horowitz, BP 156, 38042 Grenoble, France.
Ruiz
Federico
F
Cachau
Raul
R
Hazemann
Isabelle
I
Meilleur
Flora
F
Mitschler
Andre
A
Ginell
Stephan
S
Afonine
Pavel
P
Ventura
Oscar N
ON
Cousido-Siah
Alexandra
A
Haertlein
Michael
M
Joachimiak
Andrzej
A
Myles
Dean
D
Podjarny
Alberto
A
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*
D011522:Protons; D000449:Aldehyde Reductase