The Twists and Turns of Enzyme Function

We learn metabolic biochemistry largely as a series of pathways such as glycolysis, the citric acid cycle, the histidine biosynthetic pathway, etc., where each step in the pathway is catalyzed by a specific enzyme. Exceptions to this are known and are increasing. In the work by Kozmin et al. (12) directed at determining the pathway that allows Escherichia coli cells to protect themselves against toxic 6-N-hydroxylaminopurine (HAP), they have demonstrated that only the CysJ component of the sulfite reductase complex (CysJ8CysI4 or α8β4) serves along with YcbX in the reduction of HAP back to nontoxic adenine that can enter back into metabolism via a purine-salvaging pathway. Before this work, YcbX was predicted to be only a [Fe2-S2] cluster-containing protein. Their work not only confirms the function of the ycbX open reading frame in E. coli but shows that this enzyme also requires the molybdenum cofactor (MoCo) to function. The work thus demonstrates that the CysJ portion of the sulfite reductase complex can have multiple roles in cells by supplying reducing equivalents to other enzymes. This raises the possibility that other examples of redox carrier proteins functioning with multiple acceptor proteins are waiting to be discovered. This observation of multiple functions is not to be confused with so-called moonlighting enzymes, where more than one function is found in a single polypeptide chain (9), since here the enzyme is still performing the same function. Another protein implicated in this detoxification of hydroxylamines is YiiM, which the authors show also to be a MoCo-dependent enzyme but one that is not reduced by CysJ. Thus, the work also indicates the presence of two previously unknown MoCo-dependent enzymes.