The ribbon of hydrogen bonds in globular proteins. IV. The example of the papain family.

Abstract

A study of the role of the hydrogen-bonding side chains in the ribbon of hydrogen bonds in globular proteins, using the papain family as an example, suggests that these side chains may be divided into three categories depending on their position in the molecule. In the first category, they form part of the local ribbon, in the second they form part of the ribbon at a site remote along the main chain, and in the third they play no role in the formation of the ribbon. The second case is particularly interesting because it provides a natural mechanism for the formation of the tertiary structure of the globular proteins. The results suggest that the robustness of the globular proteins towards mutations arises from the fact that many mutations that involve hydrogen-bonding side chains either leave the hydrogen bonding of the ribbon essentially unchanged or their hydrogen bonding plays no part in the formation of the ribbon in the first place. The results show that it is possible to obtain the ribbon of hydrogen bonds for a family of proteins whose data set's are of intermediate quality by studying the ribbons of several members of such a family and then taking an average over the different partial ribbons to create a standard ribbon of hydrogen bonds for the family as a whole. This method is used here to derive the standard ribbon for the papain family with papain itself, actinidin, and human liver cathepsin B as the representatives of the family. All three members of the family fit the standard ribbon with an accuracy of 85-91%. This result opens up the use of this technique for the study of a large number of globular proteins whose recorded data sets are of intermediate quality.