Scientists have discovered a surprising step in enzyme catalysis by significantly expanding the utility of a standard biochemical method, according to a paper to be published online this week in Nature Chemical Biology. This advance will have major implications in understanding enzyme action and drug design.
Enzymes, or catalytic proteins, are finely tuned to help a specific chemical reaction occur very quickly. This usually means that it is hard or impossible to ‘see’ what is happening to the chemical during the catalytic steps. It is particularly difficult to see these chemical ‘intermediates’ in cases where the enzyme itself is very large, as that normally limits the range of techniques that can be used.
Tadhg Begley and colleagues have now determined the structure of three intermediates in the biosynthesis of a form of vitamin B6, by disrupting the structure of the very large enzyme Pdx1. This allowed them to see an unusual reaction step in which the chemical lost its attachment to the protein at one atom and reconnected using a different atom. The extension of this method to large proteins opens new doors in understanding other biosynthetic pathways and learning more about how drugs can and do act to change these processes.
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