Proteins, especially biomolecules such as enzymes, can exist in different structural conformations over a span of time. This property, also called conformational heterogeneity, plays an important role in helping the enzyme execute its desired functions. While crystallographic experiments conducted in a variety of environments provide crucial information about these different conformations, such results are not sufficient to understand how an enzyme recognises the substrate that it is supposed to bind to. Bhupendra Dandekar, a graduate student in Jagannath Mondal’s group investigated how the enzyme Cytochrome P450cam recognises its substrate, camphor.
Cytochrome P450cam exists in diverse and contrasting structural conformations when not bound to camphor. Dandekar conducted molecular dynamics simulations to find out the structural differences between the reported conformations of the Cytochrome P450cam enzyme. He observed that even when camphor is not bound to the enzyme, there are certain subtle differences in the structure that render the substrate recognition site of the enzyme ‘closed’ or ‘open’.
With this information in mind, the researchers show that a substrate may mostly encounter an enzyme when its recognition site is ‘closed’. In such a situation, camphor binds with Cytochrome P450cam and in this process, induces a change in the structure of the enzyme.
This study predicts a statistical probability of the instances when camphor can bind to the several contrasting structural conformations of Cytochrome P450cam, thus providing a clearer picture of the substrate recognition process.
The publication is available here.
Content: Anusheela Chatterjee