Inhibition of Saccharomyces cerevisiae phosphomannose isomerase by the NO-donor S-nitroso-acetyl-penicillamine

Phosphomannose isomerase (PMI; EC. 5.3.1.8) is an essential metalloenzyme i n the early steps of the protein glycosylation pathway in both prokaryotes and eukaryotes. The Cys150 residue (according to Candida albicans PMI numbe ring) is conserved in the active centre of mammalian and yeast PMI, but not in bacterial species where it is replaced by Asn. Here, the dose- and time -dependent inhibitory effect of the NO-donor S-nitroso-acetyl-penicillamine on the Saccharomyces cerevisiae PMI catalytic activity is reported. The an alysis of the X-ray crystal structure of C. albicans PMI and of the molecul ar model of S. cerevisiae PMI provides a rationale for the low reactivity o f Cys150 towards alkylating and nitrosylating agents.