Proceedings of the National Academy of Sciences · 2008 · 80 citations · 18 references
Life SciencesBiochemistryChemistryCatalysisEnzyme MechanismEnzymologyCatalytic MechanismsEnzyme CatalysisEnzyme CharacterizationEnzyme FunctionEnzyme StructureStructural EnzymologyCatalytic ActivityEnzyme Mechanism ModelingHydrogen Bonds In Enzyme CatalysisMechanistic EnzymologyPromiscuous CatalysisQuantum Mechanical ModelSingle-crystal Neutron DiffractionSingle-crystal X-ray Diffraction
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.
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