摘要
Enzymes can carry out effective rate accelerations by virtue of their ability to utilize substrate-channeling forces to act as a mechanochemical valve. Such a channeling process is treated quantitatively using the key aspects of the free energy landscape; the balance between substrate positioning and conformational changes reflects the severe geometric and electronic requirements for the relatively tight transition state. The observed k cat /K M of about 10 6 M -1 s -1 for PGH 2 cyclization has been revealed to be brought about by bringing together two properly oriented reactants of substrate and enzyme regarding the magnitude significance of the contribution from outer- and inner-binding stereopopulation along the free-energy channeling pathway and thus shapes the cascade cyclization route, enforcing precise spatial and temporal control. The apparent constant k cat of many P450 reactions involving the heme catalytic cycle, which is often on the order of 10 1 -10 2 s -1 and is usually attributed to compound 0 to compound I formation, may be in large part a consequence of channeling conformation changes toward the rate-limiting state that is made possible by preorganizing the proximal hydrogen-bonding pattern of the amide groups to the cysteine sulfur, and to the push-pull modulation of the relevant heme axial ligation and activation.