Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans

The similarity in sequence between murine Man II, the rat ER a-mannosidase, and the yeast vacuolar a-mannosidase was surprising considering the distinctions between the enzymes on substrate specificity and sensitivity to alkaloid inhibitors. All three enzymes recognize the small synthetic The Journal of Cell Biology, Volume 115, 1991 substrates, p-nitrophenyl a-D-mannoside and 4-methylumbelliferyl a-D-mannoside, although with different Ks (29) . These results suggest that the region of similarity might reflect a portion of the catalytic domain involved in a-mannoside recognition . The mammalian lysosomal a-mannosidase (5) also cleaves the small synthetic a-mannoside substrates and, like Man II, is inhibited by swainsonine. When the lysosomal enzyme is cloned and the sequence is determined a comparison with the consensus sequence of the other a-mannosidases would be a critical test of the function of the consensus sequence. A match in the proposed substrate recognition region between the three disparate mammalian a-mannosidases would provide strong evidence that this region is involved in the active site of the enzymes .