InterPro domain: IPR001250

Mannose-6-phosphate isomerase or phosphomannose isomerase ( 5.3.1.8 ) (PMI) is the enzyme that catalyses the interconversion of mannose-6-phosphate and fructose-6-phosphate. In eukaryotes PMI is involved in the synthesis of GDP-mannose, a constituent of N- and O-linked glycans and GPI anchors and in prokaryotes it participates in a variety of pathways, including capsular polysaccharide biosynthesis and D-mannose metabolism. PMI's belong to the cupin superfamily whose functions range from isomerase and epimerase activities involved in the modification of cell wall carbohydrates in bacteria and plants, to non-enzymatic storage proteins in plant seeds, and transcription factors linked to congenital baldness in mammals [ 1 ]. Three classes of PMI have been defined [ 2 ].

Type I includes eukaryotic PMI and the enzyme encoded by the manA gene in enterobacteria. PMI has a bound zinc ion, which is essential for activity.

A crystal structure of PMI from Candida albicans shows that the enzyme has three distinct domains [ 3 ]. The active site lies in the central domain, contains a single essential zinc atom, and forms a deep, open cavity of suitable dimensions to contain M6P or F6P The central domain is flanked by a helical domain on one side and a jelly-roll like domain on the other.

1. JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2beta. Trends Biochem. Sci. 26, 7-9
2. Purification, cDNA cloning and heterologous expression of human phosphomannose isomerase. Eur. J. Biochem. 219, 415-23
3. The x-ray crystal structure of phosphomannose isomerase from Candida albicans at 1.7 angstrom resolution. Nat. Struct. Biol. 3, 470-9