In chlorophyll biosynthesis, the light-activated enzyme, POR (protochlorophyllide oxidoreductase), has been shown to be an excellent model system for studying the role of protein motions during catalysis. The catalytic cycle of POR is understood in detail and comprises an initial photochemical reaction, which is followed by a number of ‘dark’ steps. The latter steps in the reaction cycle have been shown to involve a series of ordered product release and substrate rebinding events and are known to require conformational changes in the protein in order to proceed. However, owing to the current lack of any structural information on the enzyme, the nature of these conformational rearrangements remains poorly understood. By contrast, there is a wealth of structural and kinetic information available on the closely related enzyme dihydrofolate reductase, which is known to have a similar catalytic mechanism to POR. Dihydrofolate reductase is able to adopt an ‘occluded’ and a ‘closed’ structure, depending on which ligand is bound in the active site, and as a result, the catalytic cycle is controlled by a ‘switching’ between these two conformations. By analogy, we suggest that a similar cycling between different conformations may be operating in POR.
Conformational Changes in the Active Site Loops of Dihydrofolate Reductase during the Catalytic Cycle
