e. Studies of enzyme mechanism utilizing structures of substrates and inhibitors

This is an archive copy of the IUCr web site dating from 2008. For current content please visit https://www.iucr.org.

Next: f. Comparisons of structures using the Up: 7. Small Structures in Biology Previous: d. Studies of molecular packing and

e. Studies of enzyme mechanism utilizing structures of substrates and inhibitors

An example of the use of structure in determining the stereochemistry of an enzymatic reaction follows. In the case of aconitase, a Krebs cycle enzyme, there are three interconvertible substrates. The structures of these -- citrate, isocitrate and cis -aconitate -- were studied as various salts. From the results it was possible to suggest a mechanism whereby one of these substrates could be converted to each of the other substrates, and the fact that the hydrogen atom removed from citrate was enzymatically incorporated into isocitrate (and vice-versa) was explained. All known features of the stereochemistry of the substrates obtained from crystal structure analyses were preserved. In addition a mechanism whereby fluorocitrate inhibits the enzyme has also been proposed. Studies on the enzyme itself are now in progress.

References

1. Glusker, J. P., J. Mol. Biol . 38 (1968) 149; Accts. Chem. Res. 13 (1980) 345.

2. Carrell, H. L., Glusker, J. P., Villafranca, J. J., Mildvan, A. S., Dummel, R. J. and Kun, E., Science 170 (1970) 1412.

Next: f. Comparisons of structures using the Up: 7. Small Structures in Biology Previous: d. Studies of molecular packing and

IUCr Webmaster