This family of mammalian enzymes, located in the Golgi system, participates in the maturation process of N-glycans that leads to formation of hybrid and complex structures. The enzymes catalyse the hydrolysis of the four (1->2)-linked alpha-D-mannose residues from the Man9GlcNAc2 oligosaccharide attached to target proteins as described in reaction (1). Alternatively, the enzymes act on the Man8GlcNAc2 isomer formed by EC 3.2.1.209, endoplasmic reticulum Man9GlcNAc2 1,2-alpha-mannosidase, as described in reaction (2). The enzymes are type II membrane proteins, require Ca2+, and use an inverting mechanism. While all three human enzymes can catalyse the reactions listed here, some of the enzymes can additionally catalyse hydrolysis in an alternative order, generating additional isomeric intermediates, although the final product is the same. The names of the isomers listed here are based on a nomenclature system proposed by Prien et al .
This family of mammalian enzymes, located in the Golgi system, participates in the maturation process of N-glycans that leads to formation of hybrid and complex structures. The enzymes catalyse the hydrolysis of the four (1->2)-linked alpha-D-mannose residues from the Man9GlcNAc2 oligosaccharide attached to target proteins as described in reaction (1). Alternatively, the enzymes act on the Man8GlcNAc2 isomer formed by EC 3.2.1.209, endoplasmic reticulum Man9GlcNAc2 1,2-alpha-mannosidase, as described in reaction (2). The enzymes are type II membrane proteins, require Ca2+, and use an inverting mechanism. While all three human enzymes can catalyse the reactions listed here, some of the enzymes can additionally catalyse hydrolysis in an alternative order, generating additional isomeric intermediates, although the final product is the same. The names of the isomers listed here are based on a nomenclature system proposed by Prien et al [7].
analogue of the minimal disaccharide substrate mannobiose. Cocrystallization and mass spectrometry data suggest that when methyl-alpha-D-lyxopyranosyl-(1',2)-alpha-D-mannopyranoside is incubated with the mannosidase for long periods of time it is cleaved and that methyl-alpha-D-lyxopyranosyl-(1',2)-alpha-D-mannopyranoside behaves as a substrate
comparison of the molecular structure of the Penicillium citrinum Golgi enzyme, and yeast and human endoplasmic reticulum enzymes. There is a greater degree of freedom to bind the oligosaccharide in the active site of the fungal enzyme than in the yeast and human ER alpha1,2-mannosidases
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with the substrate analogue methyl-alpha-D-lyxopyranosyl-(1',2)-alpha-D-mannopyranoside, to 1.95 A resolution. The intact disaccharide spans the ?1/+1 subsites, with the D-lyxoside ring in the -1 subsite in the 1C4 chair conformation.The absence of the C5' hydroxymethyl group on the D-lyxoside moiety results in the side chain of Arg407 adopting two alternative conformations, the minor one interacting with Asp375 and the major one interacting with both the D-lyxoside and the catalytic base Glu409, thus disrupting its function
crystals of both the native protein and the protein-inhibitor complex. Superimpositions are performed with LSQMAN. Comparison with human alpha-1,2-mannosidasethiodisaccharide complex
native enzyme and in complexes with the inhibitors 1-deoxymannojirimycin and kifunensine, hanging drop vapor diffusion method, using 17-22% (w/v) polyethylene glycol 6000, 50 mM KH2PO4, pH 4.6
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA of the Penicillium citrinum alpha-1,2 mannosidase gene lacking the signal sequence is cloned downstream of the Aspergillus amylase promoter and of the aspergillopepsin signal sequence. The resulting fungal expression vector pTAPM1 is transfected into Aspergillus oryzae strain MS2
Structure of Penicillium citrinum alpha-1,2-mannosidase reveals the basis for differences in specificity of the endoplasmic reticulum and golgi class I enzymes