Algorithmic and Artificial Intelligence Methods for Protein Bioinformatics

Chapter 9

Algorithmic Frameworks for Protein Disulfide Connectivity Determination

RAHUL SINGH, WILLIAM MURAD, and TIMOTHY LEE

9.1 Introduction

Cysteine residues have a property unique among the amino acids, in that they can pair to form a covalent bond, known as a disulfide bond (SS bond). These bonds are so named because they occur when each cysteine's sulfhydryl group becomes oxidized following this the reaction:

9.1

Because disulfide bonds impose length and angle constraints on the backbone of a protein, knowledge of the location of these bonds can significantly help in understanding the space of possible stable tertiary structures into which the protein folds. The disulfide bond pattern of a protein also can have an important effect on its function. For example, Angata et al. [1] showed that the sterical structure formed by intramolecular disulfide bonds in the polysialyltransferase ST8Sia IV is critical for catalyzing the polysialylation of the neural cell adhesion molecule (NCAM). NCAM has an important role in neuronal development and regeneration. Figure 9.1 is a schematic representation of ST8Sia IV and the sialyltransferase of another gene family, ST6Gal I, showing how this contrast in disulfide bond structure impacts function. We define the disulfide connectivity determination ...