Glycoside Hydrolase Family 105 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:16:52Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Joel Weadge: /* Kinetics and Mechanism */

2020-12-02T19:36:57Z

Kinetics and Mechanism

James Stevenson at 20:39, 27 October 2019

2019-10-27T20:39:18Z

James Stevenson at 19:13, 4 September 2019

2019-09-04T19:13:50Z

James Stevenson at 19:12, 4 September 2019

2019-09-04T19:12:18Z

Joel Weadge: /* Substrate specificities */

2019-07-22T15:48:30Z

Substrate specificities

Joel Weadge: /* Family Firsts */

2019-07-22T14:59:42Z

Family Firsts

Joel Weadge: /* Catalytic Residues */

2019-07-22T14:56:30Z

Catalytic Residues

Joel Weadge: /* Catalytic Residues */

2019-07-22T14:54:46Z

Catalytic Residues

Joel Weadge: /* Substrate specificities */

2019-07-22T14:47:28Z

Substrate specificities

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 {{CuratorApproved}}
-* [[Author]]: ^^^James Stevenson^^^
+* [[Author]]: [[User:James Stevenson|James Stevenson]]
-* [[Responsible Curator]]: ^^^Joel Weadge^^^
+* [[Responsible Curator]]: [[User:Joel Weadge|Joel Weadge]]
 ----

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 GH105 enzymes do not act via a typical Koshland retaining or inverting mechanism <cite>Koshland1953</cite>, rather the current proposed mechanism of action for these enzymes is hydrolysis through syn-hydration of the double bond between the C-4 and C-5 carbons of the enopyranuronosyl residue of their substrate <cite>Itoh2006</cite>. This hydration reaction forms a hemiketal that undergoes spontaneous rearrangement to form an intermediate hemiacetyl, which undergoes further rearrangement resulting in the breakage of the bond to the neighbouring saccharide (at the +1 subsite of the enzyme) of the polymer. This mechanism was initially theorized based on the oligosaccharide and amino acid arrangement in a substrate-bound crystal structure <cite>Itoh2006-1</cite>, but has been confirmed through kinetic isotope effects and NMR analysis in the highly related unsaturated glucuronyl hydrolase family [[GH88]] <cite>Jongkees2011 Jongkees2014</cite>.
-The kinetics for three enzymes from the GH105 family have been determined, two from ''Bacillus subtilis'' and one from ''Bacteriodes thetaiotaomicron''. YteR from ''B. subtilis'' was found to have a ''k''<sub>cat</sub> and ''K''<sub>M</sub> of 0.2±0.011 s<sup>-1</sup> and 100±14 μM , respectively, against the substrate ΔGalA-Rha; in contrast, YesR was found to have much higher values for both these kinetic parameters, 13.9±0.7 s<sup>-1</sup> and 719±75 μM for ''k''<sub>cat</sub> and ''K''<sub>M</sub>, respectively, with the same substrate <cite>Itoh2006-1</cite>. BT3687 from ''B. thetaiotaomicron'' was determined to have a ''k''<sub>cat</sub> of 0.59±0.057 s<sup>-1</sup> and a ''K''<sub>M</sub> of 71.87±12.51 μM against the substrate ΔGlcA-GlcNAc <cite>Munoz-Munoz2017</cite>.
+The kinetics for enzymes from the GH105 family have been determined. Specifically, YteR from ''Bacillus subtilis'' was found to have a ''k''<sub>cat</sub> and ''K''<sub>M</sub> of 0.2±0.011 s<sup>-1</sup> and 100±14 μM , respectively, against the substrate ΔGalA-Rha. In contrast, YesR from ''B. subtilis'' was found to have much higher values for both these kinetic parameters, 13.9±0.7 s<sup>-1</sup> and 719±75 μM for ''k''<sub>cat</sub> and ''K''<sub>M</sub>, respectively, with the same substrate <cite>Itoh2006-1</cite>. BT3687 from ''B. thetaiotaomicron'' was determined to have a ''k''<sub>cat</sub> of 0.59±0.057 s<sup>-1</sup> and a ''K''<sub>M</sub> of 71.87±12.51 μM against the substrate ΔGlcA-GlcNAc <cite>Munoz-Munoz2017</cite>.
 Although it is atypical for a glycoside hydrolase family to contain enzymes capable of degrading both α- or β-linked substrates, this has also been observed in other families that deviate significantly from typical acid-base mechanisms (''e.g.'' [[GH3]], [[GH4]]) <cite>Rye2000</cite>.

@@ Line 37: / Line 37: @@
 GH105 enzymes do not act via a typical Koshland retaining or inverting mechanism <cite>Koshland1953</cite>, rather the current proposed mechanism of action for these enzymes is hydrolysis through syn-hydration of the double bond between the C-4 and C-5 carbons of the enopyranuronosyl residue of their substrate <cite>Itoh2006</cite>. This hydration reaction forms a hemiketal that undergoes spontaneous rearrangement to form an intermediate hemiacetyl, which undergoes further rearrangement resulting in the breakage of the bond to the neighbouring saccharide (at the +1 subsite of the enzyme) of the polymer. This mechanism was initially theorized based on the oligosaccharide and amino acid arrangement in a substrate-bound crystal structure <cite>Itoh2006-1</cite>, but has been confirmed through kinetic isotope effects and NMR analysis in the highly related unsaturated glucuronyl hydrolase family [[GH88]] <cite>Jongkees2011 Jongkees2014</cite>.
-The kinetics for three enzymes from the GH105 family have been determined, two from ''Bacillus subtilis'' and one from ''Bacteriodes thetaiotaomicron''. YteR from ''B. subtilis'' was found to have a ''k''<sub>cat</sub> and ''K''<sub>M</sub> of 0.2±0.011 s<sup>-1</sup> and 100±14μM , respectively, against the substrate ΔGalA-Rha; in contrast, YesR was found to have much higher values for both these kinetic parameters, 13.9±0.7 s<sup>-1</sup> and 719±75 μM for ''k''<sub>cat</sub> and ''K''<sub>M</sub>, respectively, with the same substrate <cite>Itoh2006-1</cite>. BT3687 from ''B. thetaiotaomicron'' was determined to have a ''k''<sub>cat</sub> of 0.59±0.057 s<sup>-1</sup> and a ''K''<sub>M</sub> of 71.87±12.51 μM against the substrate ΔGlcA-GlcNAc <cite>Munoz-Munoz2017</cite>.
+The kinetics for three enzymes from the GH105 family have been determined, two from ''Bacillus subtilis'' and one from ''Bacteriodes thetaiotaomicron''. YteR from ''B. subtilis'' was found to have a ''k''<sub>cat</sub> and ''K''<sub>M</sub> of 0.2±0.011 s<sup>-1</sup> and 100±14 μM , respectively, against the substrate ΔGalA-Rha; in contrast, YesR was found to have much higher values for both these kinetic parameters, 13.9±0.7 s<sup>-1</sup> and 719±75 μM for ''k''<sub>cat</sub> and ''K''<sub>M</sub>, respectively, with the same substrate <cite>Itoh2006-1</cite>. BT3687 from ''B. thetaiotaomicron'' was determined to have a ''k''<sub>cat</sub> of 0.59±0.057 s<sup>-1</sup> and a ''K''<sub>M</sub> of 71.87±12.51 μM against the substrate ΔGlcA-GlcNAc <cite>Munoz-Munoz2017</cite>.
 Although it is atypical for a glycoside hydrolase family to contain enzymes capable of degrading both α- or β-linked substrates, this has also been observed in other families that deviate significantly from typical acid-base mechanisms (''e.g.'' [[GH3]], [[GH4]]) <cite>Rye2000</cite>.

@@ Line 45: / Line 45: @@
 == Three-dimensional structures ==
-A number of crystal structures of GH105 unsaturated glucuronyl hydrolases expressed in bacteria have been solved, including several structures from ''B. subtilis'' <cite>Zhang2009 Itoh2006 Itoh2006-1</cite>([{{PDBlink}}1NC5 PDB ID 1NC5]), and ''B. thetaiotaomicron'' <cite>Munoz-Munoz2017 Collen2014</cite>([{{PDBlink}}3K11 PDB ID 3K11]), as well as one each from ''Bacteriodes vulgatus''  ([{{PDBlink}}4Q88 PDB ID 4Q88]), ''Clostridium acetobutylicum'' <cite>Germane2015</cite>, ''Klebsiella pneumoniae''  ([{{PDBlink}}3PMM PDB ID 3PMM]), and ''Salmonella enterica''  ([{{PDBlink}}3QWT PDB ID 3QWT]). A single enzyme from the fungus ''Thielavia terrestris'' has also been solved ([{{PDBlink}}4XUV PDB ID 4XUV]). All of these enzymes share an (α/α)6-barrel structure (also similar to that of the related GH88 enzymes), with the main differences being seen in the structure of the loop region that determines the architecture of the binding site. At the bottom of the active site pocket is a conserved WxRxxGW motif, with the tryptophan and arginine residues forming a pocket that engages the carboxyl group on the ΔGalA/GlcA monosaccharide of the -1 subsite <cite>Itoh2006</cite>. While several residues may be conserved in sequence and position at the -1 subsite, the +1 subsite is much more variable, which likely accounts for the ability of this enzyme family to catalyze the hydrolysis of polysaccharides containing α- or β-bonds linked to the C-2, -4, or -6 carbon of the +1 saccharide <cite>Collen2014</cite>.
+A number of crystal structures of GH105 unsaturated glucuronyl hydrolases expressed in bacteria have been solved, including several structures from ''B. subtilis'' <cite>Zhang2009 Itoh2006 Itoh2006-1</cite>([{{PDBlink}}1NC5 PDB ID 1NC5]), and ''B. thetaiotaomicron'' <cite>Munoz-Munoz2017 Collen2014</cite>([{{PDBlink}}3K11 PDB ID 3K11]), as well as one each from ''Bacteriodes vulgatus''  ([{{PDBlink}}4Q88 PDB ID 4Q88]), ''Clostridium acetobutylicum'' <cite>Germane2015</cite>, ''Klebsiella pneumoniae''  ([{{PDBlink}}3PMM PDB ID 3PMM]), and ''Salmonella enterica''  ([{{PDBlink}}3QWT PDB ID 3QWT]). A single enzyme from the fungus ''Thielavia terrestris'' has also been solved ([{{PDBlink}}4XUV PDB ID 4XUV]). All of these enzymes share an (α/α)6-barrel structure (also similar to that of the related GH88 enzymes), with the main differences being seen in the structure of the loop region that determines the architecture of the binding site. At the bottom of the active site pocket is a conserved WxRxxxW motif, with the tryptophan and arginine residues forming a pocket that engages the carboxyl group on the ΔGalA/GlcA monosaccharide of the -1 subsite <cite>Itoh2006</cite>. While several residues may be conserved in sequence and position at the -1 subsite, the +1 subsite is much more variable, which likely accounts for the ability of this enzyme family to catalyze the hydrolysis of polysaccharides containing α- or β-bonds linked to the C-2, -4, or -6 carbon of the +1 saccharide <cite>Collen2014</cite>.
 == Family Firsts ==

@@ Line 32: / Line 32: @@
 == Substrate specificities ==
-GH105 enzymes are a class of unsaturated glucuronyl/galacturonyl hydrolases found mainly in bacteria, but a few fungal and a handful of archaeal enzymes have also been annotated <cite>Cantarel2009</cite>. Much like the [[Glycoside Hydrolase Family 88]], enzymes from GH105 perform hydrolysis via a hydration of the double bond between the C-4 and C-5 carbons of the terminal monosaccharide of their substrates <cite>Munoz-Munoz2017 Jongkees2011</cite>. Enzymes from GH105 have been organized into three subgroups: unsaturated rhamnogalacturonidases, D-4,5-unsaturated β-glucuronyl hydrolases, and D-4,5-unsaturated α-galacturonidases. The unifying feature shared between these substrates is the presence of the non-reducing monosaccharide 4-deoxy-L-threo-hex-4-enopyranuronosyl that binds at the -1 active site of the enzymes and is linked to the +1 sugar via its anomeric C-1 carbon. The 4-deoxy-L-threo-hex-4-enopyranuronosyl saccharide can be inferred as ΔGal or ΔGlc depending on whether it assumes an α- or β- configuration, respectively, at the anomeric C-1 carbon. In degradable substrates, the sugar present at the +1 position can be linked via its C-2, C-4, or C-6 carbon, given the substrate preference of individual enzymes <cite>Zhang2009 Munoz-Munoz2017</cite>. Some of the various carbohydrate sources targeted by GH105 enzymes include: rhamnogalacturonan-I, ulvan, and the arabinogalactan decoration on certain cell wall proteins <cite>Itoh2006 Itoh2006-1 Collen2014 Munoz-Munoz2017</cite>.
+GH105 enzymes are a class of unsaturated glucuronyl/galacturonyl hydrolases found mainly in bacteria, but a few fungal and a handful of archaeal enzymes have also been annotated <cite>Cantarel2009</cite>. Much like the [[Glycoside Hydrolase Family 88]], enzymes from GH105 perform hydrolysis via a hydration of the double bond between the C-4 and C-5 carbons of the terminal monosaccharide of their substrates <cite>Munoz-Munoz2017 Jongkees2011</cite>. Enzymes from GH105 have been organized into three subgroups: unsaturated rhamnogalacturonidases, D-4,5-unsaturated β-glucuronyl hydrolases, and D-4,5-unsaturated α-galacturonidases. The unifying feature shared between these substrates is the presence of the non-reducing monosaccharide 4-deoxy-L-threo-hex-4-enopyranuronosyl that binds at the -1 active site of the enzymes and is linked to the +1 sugar via its anomeric C-1 carbon. The 4-deoxy-L-threo-hex-4-enopyranuronosyl saccharide can be inferred as ΔGalA or ΔGlcA depending on whether it assumes an α- or β- configuration, respectively, at the anomeric C-1 carbon. In degradable substrates, the sugar present at the +1 position can be linked via its C-2, C-4, or C-6 carbon, given the substrate preference of individual enzymes <cite>Zhang2009 Munoz-Munoz2017</cite>. Some of the various carbohydrate sources targeted by GH105 enzymes include: rhamnogalacturonan-I, ulvan, and the arabinogalactan decoration on certain cell wall proteins <cite>Itoh2006 Itoh2006-1 Collen2014 Munoz-Munoz2017</cite>.
 == Kinetics and Mechanism ==
 GH105 enzymes do not act via a typical Koshland retaining or inverting mechanism <cite>Koshland1953</cite>, rather the current proposed mechanism of action for these enzymes is hydrolysis through syn-hydration of the double bond between the C-4 and C-5 carbons of the enopyranuronosyl residue of their substrate <cite>Itoh2006</cite>. This hydration reaction forms a hemiketal that undergoes spontaneous rearrangement to form an intermediate hemiacetyl, which undergoes further rearrangement resulting in the breakage of the bond to the neighbouring saccharide (at the +1 subsite of the enzyme) of the polymer. This mechanism was initially theorized based on the oligosaccharide and amino acid arrangement in a substrate-bound crystal structure <cite>Itoh2006-1</cite>, but has been confirmed through kinetic isotope effects and NMR analysis in the highly related unsaturated glucuronyl hydrolase family [[GH88]] <cite>Jongkees2011 Jongkees2014</cite>.
-The kinetics for three enzymes from the GH105 family have been determined, two from ''Bacillus subtilis'' and one from ''Bacteriodes thetaiotaomicron''. YteR from ''B. subtilis'' was found to have a ''k''<sub>cat</sub> and ''K''<sub>M</sub> of 0.2±0.011 s<sup>-1</sup> and 100±14μM , respectively, against the substrate ΔGal-Rha; in contrast, YesR was found to have much higher values for both these kinetic parameters, 13.9±0.7 s<sup>-1</sup> and 719±75 μM for ''k''<sub>cat</sub> and ''K''<sub>M</sub>, respectively, with the same substrate <cite>Itoh2006-1</cite>. BT3687 from ''B. thetaiotaomicron'' was determined to have a ''k''<sub>cat</sub> of 0.59±0.057 s<sup>-1</sup> and a ''K''<sub>M</sub> of 71.87±12.51 μM against the substrate ΔGlc-GlcNAc <cite>Munoz-Munoz2017</cite>.
+The kinetics for three enzymes from the GH105 family have been determined, two from ''Bacillus subtilis'' and one from ''Bacteriodes thetaiotaomicron''. YteR from ''B. subtilis'' was found to have a ''k''<sub>cat</sub> and ''K''<sub>M</sub> of 0.2±0.011 s<sup>-1</sup> and 100±14μM , respectively, against the substrate ΔGalA-Rha; in contrast, YesR was found to have much higher values for both these kinetic parameters, 13.9±0.7 s<sup>-1</sup> and 719±75 μM for ''k''<sub>cat</sub> and ''K''<sub>M</sub>, respectively, with the same substrate <cite>Itoh2006-1</cite>. BT3687 from ''B. thetaiotaomicron'' was determined to have a ''k''<sub>cat</sub> of 0.59±0.057 s<sup>-1</sup> and a ''K''<sub>M</sub> of 71.87±12.51 μM against the substrate ΔGlcA-GlcNAc <cite>Munoz-Munoz2017</cite>.
 Although it is atypical for a glycoside hydrolase family to contain enzymes capable of degrading both α- or β-linked substrates, this has also been observed in other families that deviate significantly from typical acid-base mechanisms (''e.g.'' [[GH3]], [[GH4]]) <cite>Rye2000</cite>.
@@ Line 45: / Line 45: @@
 == Three-dimensional structures ==
-A number of crystal structures of GH105 unsaturated glucuronyl hydrolases expressed in bacteria have been solved, including several structures from ''B. subtilis'' <cite>Zhang2009 Itoh2006 Itoh2006-1</cite>([{{PDBlink}}1NC5 PDB ID 1NC5]), and ''B. thetaiotaomicron'' <cite>Munoz-Munoz2017 Collen2014</cite>([{{PDBlink}}3K11 PDB ID 3K11]), as well as one each from ''Bacteriodes vulgatus''  ([{{PDBlink}}4Q88 PDB ID 4Q88]), ''Clostridium acetobutylicum'' <cite>Germane2015</cite>, ''Klebsiella pneumoniae''  ([{{PDBlink}}3PMM PDB ID 3PMM]), and ''Salmonella enterica''  ([{{PDBlink}}3QWT PDB ID 3QWT]). A single enzyme from the fungus ''Thielavia terrestris'' has also been solved ([{{PDBlink}}4XUV PDB ID 4XUV]). All of these enzymes share an (α/α)6-barrel structure (also similar to that of the related GH88 enzymes), with the main differences being seen in the structure of the loop region that determines the architecture of the binding site. At the bottom of the active site pocket is a conserved WxRxxGW motif, with the tryptophan and arginine residues forming a pocket that engages the carboxyl group on the ΔGal/Glc monosaccharide of the -1 subsite <cite>Itoh2006</cite>. While several residues may be conserved in sequence and position at the -1 subsite, the +1 subsite is much more variable, which likely accounts for the ability of this enzyme family to catalyze the hydrolysis of polysaccharides containing α- or β-bonds linked to the C-2, -4, or -6 carbon of the +1 saccharide <cite>Collen2014</cite>.
+A number of crystal structures of GH105 unsaturated glucuronyl hydrolases expressed in bacteria have been solved, including several structures from ''B. subtilis'' <cite>Zhang2009 Itoh2006 Itoh2006-1</cite>([{{PDBlink}}1NC5 PDB ID 1NC5]), and ''B. thetaiotaomicron'' <cite>Munoz-Munoz2017 Collen2014</cite>([{{PDBlink}}3K11 PDB ID 3K11]), as well as one each from ''Bacteriodes vulgatus''  ([{{PDBlink}}4Q88 PDB ID 4Q88]), ''Clostridium acetobutylicum'' <cite>Germane2015</cite>, ''Klebsiella pneumoniae''  ([{{PDBlink}}3PMM PDB ID 3PMM]), and ''Salmonella enterica''  ([{{PDBlink}}3QWT PDB ID 3QWT]). A single enzyme from the fungus ''Thielavia terrestris'' has also been solved ([{{PDBlink}}4XUV PDB ID 4XUV]). All of these enzymes share an (α/α)6-barrel structure (also similar to that of the related GH88 enzymes), with the main differences being seen in the structure of the loop region that determines the architecture of the binding site. At the bottom of the active site pocket is a conserved WxRxxGW motif, with the tryptophan and arginine residues forming a pocket that engages the carboxyl group on the ΔGalA/GlcA monosaccharide of the -1 subsite <cite>Itoh2006</cite>. While several residues may be conserved in sequence and position at the -1 subsite, the +1 subsite is much more variable, which likely accounts for the ability of this enzyme family to catalyze the hydrolysis of polysaccharides containing α- or β-bonds linked to the C-2, -4, or -6 carbon of the +1 saccharide <cite>Collen2014</cite>.
 == Family Firsts ==

@@ Line 51: / Line 51: @@
 ; First catalytic residue identification: Crystal structure analysis of the ''B. subtilis'' YteR enzyme complexed with a ΔGlc-GalNac substrate analog suggested Asp143 is responsible for initiating the hydration reaction and  kinetic assessment of a D143N mutant of YteR  showed complete loss of catalytic activity <cite>Itoh2006-1</cite>.
 ; First evidence of hydration-based mechanism: While the mechanism of GH105 enzymes has not been fully described, the mechanism of the unsaturated glucuronyl hydrolase (UGL) from ''Clostridium perfringens'' (a closely-related GH88 protein) was determined via NMR using a methyl ketal intermediate analogue and monitoring of the reaction product during enzyme-substrate incubation in D<sub>2</sub>O <cite>Jongkees2011</cite>.
-; First 3-D structure: The 1.6Å crystal structure of the ''B. subtilis'' protein YteR, initially predicted to be a lyase-type enzyme, was reported in 2005 <cite>Zhang2009</cite>.
+; First 3-D structure: The 1.6Å crystal structure of the ''B. subtilis'' protein YteR ([{{PDBlink}}1NC5 PDB ID 1NC5]), initially predicted to be a lyase-type enzyme, was reported in 2005 <cite>Zhang2009</cite>.
 == References ==

@@ Line 42: / Line 42: @@
 == Catalytic Residues ==
-A single aspartate residue has been proposed to be responsible for the hydration reaction based on substrate-complexed X-ray crystal structures, sequence conservation, and site-directed mutagenesis <cite>Itoh2006 Itoh2006-1</cite>. The first enzyme classified into the GH105 family ([{{PDBlink}}1NC5 PDB ID 1NC5] from ''B. subtilis'') was originally predicted to be a lyase based on 65% amino acid sequence similarity and over 60% matching secondary-structure characteristics with an ''N''-acyl-D-glucosamine 2-epimerase <cite>Zhang2009</cite>. Following sequence comparison to a GH88 hydrolase (a ''B. subtilis'' UGL enzyme), and additional functional characterization, 1NC5 was determined to possess unsaturated galacturonyl hydrolase activity <cite>Itoh2006-1</cite>. A conserved aspartate residue (D143), was found to be the most likely candidate for initiating the hydration reaction, while a second conserved residue, histidine (H189), serves to correctly position a water molecule for deprotonation and addition to the C-5 carbon of the monosaccharide in the enzyme's -1 subsite <cite>Itoh2006-1</cite>. Based on sequence alignment and structural analysis, an arginine residue may take the place of this histidine residue in some GH105 enzymes (e.g. [{{PDBlink}}4CE7 PDB ID 4CE7] and [{{PDBlink}}5NOA PDB ID 5NOA]) <cite>Pettersen2004 Collen2014 Munoz-Munoz2017</cite>.
+A single aspartate residue has been proposed to be responsible for the hydration reaction based on substrate-complexed X-ray crystal structures, sequence conservation, and site-directed mutagenesis <cite>Itoh2006 Itoh2006-1</cite>. The first enzyme classified into the GH105 family (YteR; [{{PDBlink}}1NC5 PDB ID 1NC5] from ''B. subtilis'') was originally predicted to be a lyase based on 65% amino acid sequence similarity and over 60% matching secondary-structure characteristics with an ''N''-acyl-D-glucosamine 2-epimerase <cite>Zhang2009</cite>. Following sequence comparison to a GH88 hydrolase (a ''B. subtilis'' UGL enzyme), and additional functional characterization, YteR was determined to possess unsaturated galacturonyl hydrolase activity <cite>Itoh2006-1</cite>. A conserved aspartate residue (D143), was found to be the most likely candidate for initiating the hydration reaction, while a second conserved residue, histidine (H189), serves to correctly position a water molecule for deprotonation and addition to the C-5 carbon of the monosaccharide in the enzyme's -1 subsite <cite>Itoh2006-1</cite>. Based on sequence alignment and structural analysis, an arginine residue may take the place of this histidine residue in some GH105 enzymes (e.g. [{{PDBlink}}4CE7 PDB ID 4CE7] and [{{PDBlink}}5NOA PDB ID 5NOA]) <cite>Pettersen2004 Collen2014 Munoz-Munoz2017</cite>.
 == Three-dimensional structures ==