Elucidating the difference in structure and enzymatic activity of the homologues GSTO1 and CLIC1.

The Glutathione-S-Transferase superfamily are a widespread collection of enzymes that catalyse glutathione conjugation to various compounds as well as wide range of other functions. Chloride intracellular channel protein 1 is known to be a structural homologue of Omega glutathione-S-transferase 1 an enzyme belonging to the omega subclass of this superfamily. GSTO1 is a soluble enzyme thought to have a role in the glutathionylation cycle whereas CLIC1 belongs to a special class of metamorphic proteins. CLIC1 has the ability to switch from its soluble form which is homologous to GSTO1 to a membrane bound form that oligomerises to create an ion channel. The mechanism for this is insertion is not well understood. By comparing the crystal and in-solution structures of these two proteins some notable differences were discovered. With the help of SAXS the in-solution structure of CLIC1 was found not to match that of its X-ray crystal structure unlike GSTO1. Further analysis of the proline rich 'footloop' found in CLIC1 also highlighted it as an area that could potentially act as a hinge and allow for conformational change in CLIC1. This difference in structure between the two proteins could explain how CLIC1 can change shape and GSTO1 cannot. Analysis of their enzymatic properties was also carried out but the data gathered was less conclusive due to the lack of assignment for the GSTO1 protein.