Disease relevance of alpha-Man-II

• Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells [1].

High impact information on alpha-Man-II

• The crystal structure of Drosophila Golgi alpha-mannosidase II in the absence and presence of the anti-cancer agent swainsonine and the inhibitor deoxymannojirimycin reveals a novel protein fold with an active site zinc intricately involved both in the substrate specificity of the enzyme and directly in the catalytic mechanism [1].
• Glycan profiles change during normal development consistent with increasing alpha-mannosidase II and core fucosyl-transferase enzyme activities, and with decreasing activity of the Fused lobes processing hexosaminidase [2].
• The family 38 golgi alpha-mannosidase II, thought to cleave mannosidic bonds through a double displacement mechanism involving a reaction intermediate, is a clinically important enzyme involved in glycoprotein processing [3].
• Structural basis of the inhibition of golgi alpha-mannosidase II by mannostatin A and the role of the thiomethyl moiety in ligand-protein interactions [4].
• The X-ray crystal structures of mannose trimming enzyme drosophila Golgi alpha-mannosidase II (dGMII) complexed with the inhibitors mannostatin A (1) and an N-benzyl analogue (2) have been determined [4].

Biological context of alpha-Man-II

• GmII has been localized to a single site (85D14-18) on the right arm of chromosome 3 [5].
• Using the murine cDNA that encodes Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase; EC 3.2.1.114) as a probe to screen a cDNA library made from Drosophila melanogaster (Dm) embryos, we have isolated GmII, the Dm sequence homologue [5].
• Inhibition of Golgi mannosidase II with mannostatin A analogues: synthesis, biological evaluation, and structure-activity relationship studies [6].

Anatomical context of alpha-Man-II

• Treatment with brefeldin A (BFA) resulted in the redistribution of rArl1 and mannosidase II into the cytoplasm and endoplasmic reticulum, respectively [7].
• Co-localization experiments in NRK cells with antibodies to mannosidase II and a newly identified cis-Golgi protein, p28, showed that rArl1 is localized to the Golgi complex [7].

Associations of alpha-Man-II with chemical compounds

• When cells were treated with nocodazole, the Golgi complex marked by mannosidase II and p28 was fragmented into punctate structures scattered throughout the cell, in which rArl1 was colocalized [7].
• In this paper, the 1.80 A resolution crystal structure of kifunensine bound to Drosophila melanogaster Golgi alpha-mannosidase II (dGMII) is presented [8].
• Differing conformations of 1-deoxymannojirimycin were also observed: a (4)C(1) and (1)C(4) conformation in dGMII and hERMI, respectively [8].
• Kifunensine adopts a (1,4)B boat conformation in the class II dGMII, which contrasts the (1)C(4) chair conformation seen in class I human endoplasmic reticulum alpha1,2 mannosidase (hERMI, PDB ) [8].
• It was found that mannostatin and aminocyclopentitretrol could bind to Golgi alpha-mannosidase II in a similar mode to that of the known inhibitor swainsonine [6].

Analytical, diagnostic and therapeutic context of alpha-Man-II

• Cloning and sequence analysis of GmII, a Drosophila melanogaster homologue of the cDNA encoding murine Golgi alpha-mannosidase II [5].

References