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Dolicholphosphate Mannosyltransferase: A Glycosyltransferase with Unity in Molecular Diversities
Author(s) -
Baksi Krishna,
Zhang Zhenbo,
Banerjee Dipak K
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.951.1
Subject(s) - glycosyltransferase , glycosylation , biochemistry , biology , endoplasmic reticulum , peptide sequence , transmembrane protein , sequence motif , glycan , amino acid , biosynthesis , gene , glycoprotein , receptor
N‐glycan provides structural and functional stability to glycoproteins and adds to their flexibility. Glycan biosynthesis is elaborative, multi‐compartmental and uses glycosyltransferases. Failure to assemble N‐glycan leads to phenotypic changes developing infection, cancer, congenital disorders of glycosylation (CDGs) among others. The biosynthetic process begins at the endoplasmic reticulum (ER) with the assembly of dolichol‐linked tetradecasaccharide Glc 3 Man 9 GlcNAc 2 ‐PP‐Dol where DPMS plays a critical role. DPMS is also essential for GPI anchor biosynthesis, protein O‐mannosylation in yeast as well as O‐ and C‐mannosylation in eukaryotes. DPMS has been purified from several species and its gene has been cloned from 40 species (protozoan parasite to human). The sequence alignment indicates the presence of a cAMP‐dependent protein phosphorylation motif (PKA motif) in DPMS from 39 species. Hydrophobicity analysis of the DPMS sequence from bovine, human , S. crevisiae and A. thaliana all show the PKA motif each preceded and succeeded by a sequence of hydrophobic amino acid residues, i.e., the presence of a transmembrane domain. Irrespective of these similarities, the amino acid sequence at the C‐terminus and the kinetic behavior have classified DPMS as Type I and Type II enzyme. DPMS belonging to Type II sub‐class has been proposed to be a multimeric protein requiring DPM2 and DPM3 to anchor down DPM1 to the ER membrane. Based on the hydrophobicity as well as the successful expression of bovine DPM1 gene in E. coli we conclude that the logic proposing the above model needs to be revisited. Because of inherent diversities, DPMS has acquired sensing ability of cellular microenvironment and can serve as an excellent biosensor. In addition, DPMS activity is down regulated during aging but when upregulated in capillary endothelial cells due to activation of β‐adrenoreceptor angiogenesis, a hallmark of tumor growth is enhanced. Furthermore, DPMS from rat liver, rat parotid acinar cells, hen oviduct, bovine brain as well as from S. cerevisiae all showed increased activity upon phosphorylation in vitro . Support or Funding Information The work was partly supported by funds from NIH/NIMHD G12MD007583 (KB), NIH U54‐CA096297, Susan G. Komen for the Cure BCTR0600582, and NSF EPS‐1002410 (DKB).