Carbohydrate Binding Module Family 94 - Revision history

Elizabeth Ficko-Blean: /* Family Firsts */

2023-04-13T08:53:29Z

Family Firsts

Elizabeth Ficko-Blean: /* Structural Features */

2023-04-13T08:49:13Z

Structural Features

Elizabeth Ficko-Blean: /* Structural Features */

2023-04-13T08:47:13Z

Structural Features

Elizabeth Ficko-Blean: /* Structural Features */

2023-04-13T08:45:12Z

Structural Features

Elizabeth Ficko-Blean at 08:42, 13 April 2023

2023-04-13T08:42:49Z

Takatsugu Miyazaki at 07:26, 13 April 2023

2023-04-13T07:26:32Z

Takatsugu Miyazaki at 06:01, 13 April 2023

2023-04-13T06:01:42Z

Takatsugu Miyazaki at 05:44, 13 April 2023

2023-04-13T05:44:57Z

Takatsugu Miyazaki at 05:10, 13 April 2023

2023-04-13T05:10:33Z

Takatsugu Miyazaki at 04:50, 13 April 2023

2023-04-13T04:50:17Z

@@ Line 32: / Line 32: @@
 == Family Firsts ==
-;First Identified
+;First Identified: The 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 <cite>Oka2022,Nagae2022</cite>.
-: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 <cite>Oka2022,Nagae2022</cite>.
+;First Structural Characterization: The crystal structures of the C-terminal domains of human and mouse GnT-IVa (MGAT4A) and the ''Bombyx mori'' ortholog were determined independently by two groups <cite>Oka2022,Nagae2022</cite>. A β-GlcNAc-bound structure of ''B. mori'' CBM94 was also determined <cite>Oka2022</cite>.
 == References ==

@@ Line 21: / Line 21: @@
 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 [{{EClink}}2.4.1.145 2.4.1.145], Fig. 1) and an ortholog from lepidopteran insect ''Bombyx mori'' (silkworm) <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' showed affinity toward ''N''-acetylglucosamine (GlcNAc), ''N'',''N''’-diacetylchitobiose, and ''p''-nitrophenyl β-''N''-acetylglucosaminide with ''K''<sub>a</sub> values of 242–1970 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 GlcNAc-β-(1→2)-Man 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 lower affinity for ''N''-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV <cite>Nagae2022</cite>. Therefore, GnT-IVa CBM94 prefers product ''N''-glycans to substrate ''N''-glycans (Fig. 1).
 == Structural Features ==
-CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt a β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to the [[CBM32]]s, such as the GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
+CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt a β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to the [[CBM32]]s, such as the GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of the ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
 [[File:Fig2 CBM94 structures.png|thumb|600px|center|'''Figure 2. Overall structures of CBM94 proteins.''' (Left to right) Mouse GnT-IVa CBM94 (D445A mutant) [{{PDBlink}}7VMT 7VMT], human GnT-IVa CBM94 [{{PDBlink}}7XTL 7XTL], and ''B. mori'' GnT-IV ortholog CBM94 in complex with GlcNAc (''magenta'' stick) [{{PDBlink}}7XTN 7XTN]. ]]

@@ Line 21: / Line 21: @@
 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 [{{EClink}}2.4.1.145 2.4.1.145], Fig. 1) and an ortholog from lepidopteran insect ''Bombyx mori'' (silkworm) <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' showed affinity toward ''N''-acetylglucosamine (GlcNAc), ''N'',''N''’-diacetylchitobiose, and ''p''-nitrophenyl β-''N''-acetylglucosaminide with ''K''<sub>a</sub> values of 242–1970 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 GlcNAc-β-(1→2)-Man 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 lower affinity for ''N''-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV <cite>Nagae2022</cite>. Therefore, GnT-IVa CBM94 prefers product ''N''-glycans to substrate ''N''-glycans (Fig. 1).
 == Structural Features ==
-CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt a β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to CBM32 proteins, such as a GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
+CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt a β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to the [[CBM32]]s, such as the GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
 [[File:Fig2 CBM94 structures.png|thumb|600px|center|'''Figure 2. Overall structures of CBM94 proteins.''' (Left to right) Mouse GnT-IVa CBM94 (D445A mutant) [{{PDBlink}}7VMT 7VMT], human GnT-IVa CBM94 [{{PDBlink}}7XTL 7XTL], and ''B. mori'' GnT-IV ortholog CBM94 in complex with GlcNAc (''magenta'' stick) [{{PDBlink}}7XTN 7XTN]. ]]

@@ Line 21: / Line 21: @@
 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 [{{EClink}}2.4.1.145 2.4.1.145], Fig. 1) and an ortholog from lepidopteran insect ''Bombyx mori'' (silkworm) <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' showed affinity toward ''N''-acetylglucosamine (GlcNAc), ''N'',''N''’-diacetylchitobiose, and ''p''-nitrophenyl β-''N''-acetylglucosaminide with ''K''<sub>a</sub> values of 242–1970 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 GlcNAc-β-(1→2)-Man 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 lower affinity for ''N''-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV <cite>Nagae2022</cite>. Therefore, GnT-IVa CBM94 prefers product ''N''-glycans to substrate ''N''-glycans (Fig. 1).
 == Structural Features ==
-CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to CBM32 proteins, such as a GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
+CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt a β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to CBM32 proteins, such as a GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
 [[File:Fig2 CBM94 structures.png|thumb|600px|center|'''Figure 2. Overall structures of CBM94 proteins.''' (Left to right) Mouse GnT-IVa CBM94 (D445A mutant) [{{PDBlink}}7VMT 7VMT], human GnT-IVa CBM94 [{{PDBlink}}7XTL 7XTL], and ''B. mori'' GnT-IV ortholog CBM94 in complex with GlcNAc (''magenta'' stick) [{{PDBlink}}7XTN 7XTN]. ]]

@@ Line 19: / Line 19: @@
 [[File:Fig1 GnTIV reaction.png|thumb|300px|right|'''Figure 1. Reaction catalyzed by GnT-IVa and GnT-IVb.''' [[GT54]] GnT-IVa and GnT-IVb transfer GlcNAc to β-1,2-GlcNAc-attached mannose residue of α-1,3 arm, while GnT-IVc (also known as GnT-VI) transfers GlcNAc to β-1,2-GlcNAc-attached mannose residue of α-1,6 arm in ''N''-glycans. ]]
-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 [{{EClink}}2.4.1.145 2.4.1.145], Fig. 1) and an ortholog from lepidopteran insect ''Bombyx mori'' (silkworm) <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' showed affinity toward ''N''-acetylglucosamine (GlcNAc), ''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 GlcNAc-β-(1→2)-Man 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 lower affinity for ''N''-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV <cite>Nagae2022</cite>. Therefore, GnT-IVa CBM94 prefers product ''N''-glycans to substrate ''N''-glycans (Fig. 1).
+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 [{{EClink}}2.4.1.145 2.4.1.145], Fig. 1) and an ortholog from lepidopteran insect ''Bombyx mori'' (silkworm) <cite>Oka2022</cite>. The CBM94 proteins from human and ''B. mori'' showed affinity toward ''N''-acetylglucosamine (GlcNAc), ''N'',''N''’-diacetylchitobiose, and ''p''-nitrophenyl β-''N''-acetylglucosaminide with ''K''<sub>a</sub> values of 242–1970 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 GlcNAc-β-(1→2)-Man 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 lower affinity for ''N''-glycan with only β-(1→2)-linked GlcNAc, which is the substrate of GnT-IV <cite>Nagae2022</cite>. Therefore, GnT-IVa CBM94 prefers product ''N''-glycans to substrate ''N''-glycans (Fig. 1).
 == Structural Features ==
 CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to CBM32 proteins, such as a GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.

@@ Line 25: / Line 25: @@
 [[File:Fig3 CBM94 bindingsite.png|thumb|300px|right|'''Figure 3. GlcNAc-binding sites of CBM94 proteins.''' Mouse GnT-IVa CBM94 (D445A mutant) [{{PDBlink}}7VMT 7VMT] and human GnT-IVa CBM94 [{{PDBlink}}7XTL 7XTL] are superimposed into ''B. mori'' GnT-IV ortholog CBM94 in complex with GlcNAc (''magenta'' stick) [{{PDBlink}}7XTN 7XTN]. Amino acid residues interacting with GlcNAc in ''B. mori'' CBM94 and the corresponding residues in human and mouse CBM94 are represented as stick models.]]
-CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 adopt β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to CBM32 proteins, such as a GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
+CBM94 domains of GnT-IV enzymes comprise of around 150 amino acid residues. The crystal structures of the CBM94 domains in human and mouse GnT-IVa and ''B. mori'' ortholog were determined at 1.97, 1.95, and 1.47 Å resolution (PDB ID [{{PDBlink}}7XTL 7XTL], [{{PDBlink}}7VMT 7VMT], and [{{PDBlink}}7XTM 7XTM]), respectively. The mammalian CBM94 proteins adopt β-sandwich fold comprising nine β-strands and three short α-helices, while ''B. mori'' CBM94 has a similar fold but lacks one α-helix (Fig. 2). They are structurally homologous to CBM32 proteins, such as a GlcNAc-binding [[CBM32]] domain (NagHCBM32-2) of ''Clostridium perfringens'' [[GH84]] β-''N''-acetylglucosaminidase NagH <cite>Ficko-Blean2009</cite>. The 1.15-Å resolution structure of ''B. mori'' CBM94 in complex with β-GlcNAc (PDB ID [{{PDBlink}}7XTN 7XTN]) indicates that Tyr429, Trp445, Asp480, and Trp535 contribute to GlcNAc binding (Fig. 3). These residues are completely conserved among NagHCBM32-2 and CBM94 domains in mammalian GnT-IV isozymes (GnT-IVa, GnT-IVb, and GnT-IVc) except that Tyr429 is substituted to Phe in GnT-IVc.
 == Functionalities ==
 The CBM94 domains of human GnT-IVa and ''B. mori'' ortholog were only examined for affinity to sugars, but the CBM94 domain of mouse GnT-IVa was examined for its relevance to enzyme activity and substrate specificity. The deletion of the CBM94 domain markedly reduced the activity of mouse GnT-IVa, and the replacement of Asp445, which binds GlcNAc, with Ala also reduced the glycosyltransferase activity. Based on its affinity for glycans, it is possible that the function of the CBM94 domain is to regulate the catalytic cycle from enzymatic reaction to product release rather than to capture substrates <cite>Nagae2022</cite>. A comparative study of mouse GnT-IVa and GnT-IVb suggested that their CBM94 domains affect substrate glycoprotein preference in addition to the glycan binding function <cite>Osada2022</cite>. It should be noted that a CBM94 domain is conserved among GnT-IV isozymes, GnT-IVa, -IVb, and -IVc, but is completely absent in GnT-IVd (MGAT4D), which has no enzymatic activity observed and inhibits GnT-I activity <cite>Huang2015</cite>.

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
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 * [[Author]]:  [[User:Takatsugu Miyazaki|Takatsugu Miyazaki]]
 * [[Responsible Curator]]:  [[User:Takatsugu Miyazaki|Takatsugu Miyazaki]]