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Function
Mannosidase (MAN) is an enzyme which hydrolyzes mannose. There are 2 kinds of MAN. α-MAN which hydrolyzes α-mannose[1] and β-MAN which hydrolyzes β-1,4-linked manno-oligosaccharides[2]. α-MAN isozymes are classified as class I and II.
- Mannan endo-1,4-β-MAN hydrolyzes 1-4-β-D-mannosidic linkages in mannans, galactomannans and glucomannans.
- Endo-1,2-α-MAN is the Endo-acting glycoside hydrolase involved in N-glycan trimming located in the Golgi[3]
See some details in Molecular Playground/ERMan1. See also Carbohydrate Metabolism.
Disease
α-mannosidosis is manifested by accumulation of mannose-containing oligosaccharides leading to mental retardation, hearing impairment, skeletal changes and immunodeficiency[4]. β-MAN deficiency called β-mannosidosis is a disorder of oligosaccharide metabolism[5].
Structural highlights
The active site of β-MAN contains β-mannose[6]. Water molecules shown as red spheres.
3D structures of mannosidase
Mannosidase 3D structures
- ↑ Heikinheimo P, Helland R, Leiros HK, Leiros I, Karlsen S, Evjen G, Ravelli R, Schoehn G, Ruigrok R, Tollersrud OK, McSweeney S, Hough E. The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation. J Mol Biol. 2003 Mar 28;327(3):631-44. PMID:12634058
- ↑ Ademark P, Lundqvist J, Hagglund P, Tenkanen M, Torto N, Tjerneld F, Stalbrand H. Hydrolytic properties of a beta-mannosidase purified from Aspergillus niger. J Biotechnol. 1999 Oct 8;75(2-3):281-9. PMID:10553664
- ↑ Sobala LF, Fernandes PZ, Hakki Z, Thompson AJ, Howe JD, Hill M, Zitzmann N, Davies S, Stamataki Z, Butters TD, Alonzi DS, Williams SJ, Davies GJ. Structure of human endo-alpha-1,2-mannosidase (MANEA), an antiviral host-glycosylation target. Proc Natl Acad Sci U S A. 2020 Nov 5. pii: 2013620117. doi:, 10.1073/pnas.2013620117. PMID:33154157 doi:https://dx.doi.org/10.1073/pnas.2013620117
- ↑ Berg T, Riise HM, Hansen GM, Malm D, Tranebjaerg L, Tollersrud OK, Nilssen O. Spectrum of mutations in alpha-mannosidosis. Am J Hum Genet. 1999 Jan;64(1):77-88. PMID:9915946 doi:https://dx.doi.org/S0002-9297(07)61660-7
- ↑ Uchino Y, Fukushige T, Yotsumoto S, Hashiguchi T, Taguchi H, Suzuki N, Konohana I, Kanzaki T. Morphological and biochemical studies of human beta-mannosidosis: identification of a novel beta-mannosidase gene mutation. Br J Dermatol. 2003 Jul;149(1):23-9. PMID:12890191
- ↑ Tankrathok A, Iglesias-Fernandez J, Luang S, Robinson RC, Kimura A, Rovira C, Hrmova M, Ketudat Cairns JR. Structural analysis and insights into the glycon specificity of the rice GH1 Os7BGlu26 beta-D-mannosidase. Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2124-35. doi:, 10.1107/S0907444913020568. Epub 2013 Sep 20. PMID:24100330 doi:https://dx.doi.org/10.1107/S0907444913020568
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