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Difference between revisions of "Carbohydrate Binding Module Family 94"
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== Ligand specificities == | == Ligand specificities == | ||
− | CBM94 was established in 2022 after the structural and functional characterization of the C-terminal domains of human ''N''-acetylglucosaminyltransferase IVa (GnT-IVa, MGAT4A; [[GT54]]; EC 2.4.1.145) and an ortholog from lepidopteran insect ''Bombyx mori'' <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' comprise of around 140 amino acid residues and showed affinity toward ''N''-acetylglucosamine, ''N'',''N''’-diacetylchitobiose, and ''p''-nitrophenyl β-''N''-acetylglucosaminide with ''K''<sub>a</sub> values of 242–1,970 M<sup>−1</sup>. No affinity was detected for other monosaccharides, including glucose, mannose, galactose, L-fucose, and ''N''-acetylgalactosamine, some of which are components of matured ''N''-glycans <cite>Oka2022</cite>. Nagae et al. demonstrated that the C-terminal domain of mouse GnT-IVa has binding ability for GlcNAc and GlcNAcβ1-2Man using NMR titration analysis <cite>Nagae2022</cite>. Furthermore, comprehensive frontal affinity chromatography analysis using 157 glycans showed that mouse CBM94 has affinity for ''N''-glycans with β-(1→2) and β-(1→4)-linked GlcNAc at the non-reducing ends. On the other hand, it showed low affinity for ''N''-glycan with only β-(1→2)- | + | CBM94 was established in 2022 after the structural and functional characterization of the C-terminal domains of human ''N''-acetylglucosaminyltransferase IVa (GnT-IVa, MGAT4A; [[GT54]]; EC 2.4.1.145) and an ortholog from lepidopteran insect ''Bombyx mori'' <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' comprise of around 140 amino acid residues and showed affinity toward ''N''-acetylglucosamine, ''N'',''N''’-diacetylchitobiose, and ''p''-nitrophenyl β-''N''-acetylglucosaminide with ''K''<sub>a</sub> values of 242–1,970 M<sup>−1</sup>. No affinity was detected for other monosaccharides, including glucose, mannose, galactose, L-fucose, and ''N''-acetylgalactosamine, some of which are components of matured ''N''-glycans <cite>Oka2022</cite>. Nagae et al. demonstrated that the C-terminal domain of mouse GnT-IVa has binding ability for GlcNAc and GlcNAcβ1-2Man using NMR titration analysis <cite>Nagae2022</cite>. Furthermore, comprehensive frontal affinity chromatography analysis using 157 glycans showed that mouse CBM94 has affinity for ''N''-glycans with β-(1→2) and β-(1→4)-linked GlcNAc at the non-reducing ends. On the other hand, it showed low affinity for ''N''-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV <cite>Nagae2022</cite>. Therefore, CBM94 prefers product ''N''-glycans rather than substrate ''N''-glycans. |
== Structural Features == | == Structural Features == |
Revision as of 20:26, 19 January 2023
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CAZy DB link | |
http://www.cazy.org/CBM94.html |
Ligand specificities
CBM94 was established in 2022 after the structural and functional characterization of the C-terminal domains of human N-acetylglucosaminyltransferase IVa (GnT-IVa, MGAT4A; GT54; EC 2.4.1.145) and an ortholog from lepidopteran insect Bombyx mori [1]. The CBM94 proteins from human and B. mori comprise of around 140 amino acid residues and showed affinity toward N-acetylglucosamine, N,N’-diacetylchitobiose, and p-nitrophenyl β-N-acetylglucosaminide with Ka values of 242–1,970 M−1. No affinity was detected for other monosaccharides, including glucose, mannose, galactose, L-fucose, and N-acetylgalactosamine, some of which are components of matured N-glycans [1]. Nagae et al. demonstrated that the C-terminal domain of mouse GnT-IVa has binding ability for GlcNAc and GlcNAcβ1-2Man using NMR titration analysis [2]. Furthermore, comprehensive frontal affinity chromatography analysis using 157 glycans showed that mouse CBM94 has affinity for N-glycans with β-(1→2) and β-(1→4)-linked GlcNAc at the non-reducing ends. On the other hand, it showed low affinity for N-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV [2]. Therefore, CBM94 prefers product N-glycans rather than substrate N-glycans.
Structural Features
Content in this section should include, in paragraph form, a description of:
- Fold: Structural fold (beta trefoil, beta sandwich, etc.)
- Type: Include here Type A, B, or C and properties
- Features of ligand binding: Describe CBM binding pocket location (Side or apex) important residues for binding (W, Y, F, subsites), interact with reducing end, non-reducing end, planar surface or within polysaccharide chains. Include examples pdb codes. Metal ion dependent. Etc.
Functionalities
Content in this section should include, in paragraph form, a description of:
- Functional role of CBM: Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
- Most Common Associated Modules: 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
- Novel Applications: Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.
Family Firsts
- First Identified
- Sugar-binding ability of the C-terminal domains of human and mouse GnT-IVa (MGAT4A) and Bombyx mori ortholog was identified independently by two groups [1, 2].
- First Structural Characterization
- Crystal structures of the C-terminal domains of human and mouse GnT-IVa (MGAT4A) and Bombyx mori ortholog were determined independently by two groups [1, 2]. β-GlcNAc-bound structure of B. mori CBM94 was also determined [1].
References
- Oka N, Mori S, Ikegaya M, Park EY, and Miyazaki T. (2022). Crystal structure and sugar-binding ability of the C-terminal domain of N-acetylglucosaminyltransferase IV establish a new carbohydrate-binding module family. Glycobiology. 2022;32(12):1153-1163. DOI:10.1093/glycob/cwac058 |
- Nagae M, Hirata T, Tateno H, Mishra SK, Manabe N, Osada N, Tokoro Y, Yamaguchi Y, Doerksen RJ, Shimizu T, and Kizuka Y. (2022). Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A). Commun Biol. 2022;5(1):695. DOI:10.1038/s42003-022-03661-w |
- Osada N, Nagae M, Nakano M, Hirata T, and Kizuka Y. (2022). Examination of differential glycoprotein preferences of N-acetylglucosaminyltransferase-IV isozymes a and b. J Biol Chem. 2022;298(9):102400. DOI:10.1016/j.jbc.2022.102400 |