Unusual enzyme dynamics revealed by computer simulations

Enzymes are biocatalysts of living cells, converting small molecules called substrates to their corresponding products. Enzymes are highly valued by chemical and pharmaceutical industries. Most of the enzymes perform chemical reactions deep inside themselves at precisely organized active sites. The active sites can only accommodate certain molecules which allows the enzymes to distinguish their own substrates from all the molecules in the surrounding environment. Another layer of a molecule recognition is provided by the enzyme tunnels, which connect the active sites with the surrounding environment. In this study, an enzyme with a tiny active site and narrow tunnels was noted to be able to catalyze a substrate about two times bigger in its size.

Surprised by this finding, the researchers wanted to see how this happens in the molecular level. Computational simulations of the enzyme and the big substrate showed that there are multiple tunnels from the surrounding environment to the active site. Some of these tunnels open wide by moving a helix to enable the big substrate to enter the active site. The results provide a valuable lesson in the flexibility of enzymes and provide new possibilities for engineering the part of the enzyme responsible for the tunnel opening, paving a way to design more efficient enzymes for practical use.


Piia Kokkonen – piia@mail.muni.cz
Jitka Sedlackova - jitkasedlackova@mail.muni.cz

Conformational Changes Allow Processing of Bulky Substrates by a Haloalkane Dehalogenase with a Small and Buried Active Site, Piia Kokkonen, David Bednar, Veronika Dockalova, Zbynek Prokop and Jiri Damborsky, The Journal of Biological Chemistry, in press.