Functional diversity of the phosphoglucomutase superfamily: structural implications

Three-dimensional structural models of three members of thephosphoglucomutase (PGM) superfamily, parafusin, phosphoglucomutase-relatedprotein and sarcoplasmic reticulum phosphoglucomutase, wereconstructed by homology modeling based on the known crystalstructure of rabbit muscle phosphoglucomutase. Parafusin, phosphoglucomutase-relatedprotein and sarcoplasmic reticulum phosphoglucomutase each have50% or more identity with rabbit muscle phosphoglucomutase atthe amino acid level and all are reported to exhibit no or minorphosphoglucomutase activity. There are four major insertionsand two deletions in the parafusin sequence relative to PGM,all of which are located in surface-exposed loops connectingsecondary structural elements. The remaining amino acid substitutionsare distributed throughout the sequence and are not predictedto alter the polypeptide fold. Parafusin contains a putativeprotein kinase C site located on a surface loop in domain IIthat is not present in the homologs. Although the general domainstructure and the active site of rabbit muscle phosphoglucomutaseare preserved in the model of phosphoglucomutase-related protein,a major structural difference is likely to occur in domain 1due to the absence of 55 amino acid residues in PGM-RP. Thisdeletion predicts the loss of three -helices and one ß-strandfrom an anti-parallel ß-sheet in this domain as comparedwith the rabbit muscle phosphoglucomutase.