Glycoside Hydrolase Family 70 - Revision history

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

2021-12-18T21:14:35Z

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

Stefan Janecek at 10:06, 17 June 2015

2015-06-17T10:06:31Z

Spencer Williams: /* Catalytic Residues */

2013-06-27T05:49:28Z

Catalytic Residues

Spencer Williams: /* Substrate specificities */

2012-11-26T01:39:52Z

Substrate specificities

Spencer Williams: /* Substrate specificities */

2012-11-26T01:39:27Z

Substrate specificities

Spencer Williams at 01:39, 26 November 2012

2012-11-26T01:39:02Z

Harry Brumer: /* Substrate specificities */ Changed Fig 1 to PNG format

2012-09-19T14:57:12Z

Substrate specificities: Changed Fig 1 to PNG format

Harry Brumer: /* Three-dimensional structures */ Changed Fig 2 to PNG format

2012-09-19T14:55:17Z

Three-dimensional structures: Changed Fig 2 to PNG format

Harry Brumer: /* Substrate specificities */

2012-09-07T15:04:39Z

Substrate specificities

Stefan Janecek at 16:52, 6 September 2012

2012-09-06T16:52:06Z

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 {{CuratorApproved}}
-* [[Author]]: ^^^Magali Remaud-Simeon^^^
+* [[Author]]: [[User:Magali Remaud-Simeon|Magali Remaud-Simeon]]
-* [[Responsible Curator]]s: ^^^Stefan Janecek^^^
+* [[Responsible Curator]]s: [[User:Stefan Janecek|Stefan Janecek]]
 ----

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 * dextransucrase (sucrose:1,6-α-D-glucosyltransferase; EC [{{EClink}}2.4.1.5 2.4.1.5]),
 * alternansucrase (sucrose:1,6(1,3)-α-D-glucan-6(3)-α-D-glucosyltransferase, EC [{{EClink}}2.4.1.140 2.4.1.140]),
-* mutansucrase (sucrose:1,3-α-D-glucan-3-α-D-glucosyltransferase; EC [{{EClink}}2.4.1.5 2.4.1.5]), and
+* mutansucrase (sucrose:1,3-α-D-glucan-3-α-D-glucosyltransferase; EC [{{EClink}}2.4.1.125 2.4.1.125]), and
-* reuteransucrase (sucrose:1,4(6-α-D-glucan-4(6)-α-D-glucosyltransferase; EC [{{EClink}}2.4.1.5 2.4.1.5]).
+* reuteransucrase (sucrose:1,4(6-α-D-glucan-4(6)-α-D-glucosyltransferase; EC [{{EClink}}2.4.1.- 2.4.1.-]).
 A wide range of α-D-glucans, varying in size, structure, degree of branching and spatial arrangements can thus be produced by GH70 family members <cite>Sidebotham1974,Monchois1999,Leemhuis2012,Andre2010</cite>.

@@ Line 52: / Line 52: @@
 == Catalytic Residues ==
-Sequence analysis, secondary structure prediction and tertiary structure comparison with enzymes from [[GH13]] enabled the localization of a putative catalytic triad that is strictly conserved in GH70 and similar to that found in [[GH13]] <cite>Vujicic-Zagar2010 Ito2011</Cite>. This triad is formed by an aspartate (catalytic [[nucleophile]]) corresponding to the residue identified by peptide sequencing <cite>Mooser1989,Mooser1991</Cite>, a glutamate ([[general acid/base]] catalysts) and a second aspartic acid that is critical for [[transition state]] stabilization <cite>Vujicic-Zagar2010,Ito2011</Cite>. The putative role of these residues in catalysis was further supported by mutations and structural analyses <cite>Monchois1999,Leemhuis2012,Andre2010</cite>.
+Sequence analysis, secondary structure prediction and tertiary structure comparison with enzymes from [[GH13]] enabled the localization of a putative catalytic triad that is strictly conserved in GH70 and similar to that found in [[GH13]] <cite>Vujicic-Zagar2010 Ito2011</Cite>. This triad is formed by an aspartate ([[catalytic nucleophile]]) corresponding to the residue identified by peptide sequencing <cite>Mooser1989,Mooser1991</Cite>, a glutamate ([[general acid/base]] catalysts) and a second aspartic acid that is critical for [[transition state]] stabilization <cite>Vujicic-Zagar2010,Ito2011</Cite>. The putative role of these residues in catalysis was further supported by mutations and structural analyses <cite>Monchois1999,Leemhuis2012,Andre2010</cite>.
 == Three-dimensional structures ==

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
 [[Image:Mag Fig1.png|thumb|right|400px|'''Fig. 1. Reactions catalyzed from sucrose''']]
-GH70 enzymes are [[transglycosidase|transglucosylases]] produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the [[clan]] GH-H.
+GH70 enzymes are [[transglycosidases|transglucosylases]] produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the [[clan]] GH-H.
 Most of the enzymes classified in this family use sucrose as the D-glucopyranosyl donor to synthesize α-D-glucans of high molecular mass (>10<sup>6</sup> Da) with the concomitant release of D-fructose (Fig. 1). They are also referred to as glucosyltransferases (GTF) or glucansucrases (GS) <cite>Sidebotham1974,Monchois1999,Leemhuis2012,Andre2010</cite>. The first glucansucrase was isolated from sucrose-broth cultures of a strain of ''Ln.  mesenteroides'' <Cite>Hehre1941,Hehre1942</Cite>. The enzyme was shown to synthesize water-soluble dextran (α-1,6 linked D-glucan) from sucrose alone. Dextran from ''Ln. mesenteroides'' sp. was the first microbial polysaccharide to be commercialized and used for pharmaceutical and fine chemical applications. The glucansucrases produced by ''Streptococcus'' sp. were extensively studied on account of their major role in the formation of dental caries <Cite>Sidebotham1974,Monchois1999</Cite>.

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
 [[Image:Mag Fig1.png|thumb|right|400px|'''Fig. 1. Reactions catalyzed from sucrose''']]
-GH70 enzymes are [[transglycosylase|transglucosylases]] produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the [[clan]] GH-H.
+GH70 enzymes are [[transglycosidase|transglucosylases]] produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the [[clan]] GH-H.
 Most of the enzymes classified in this family use sucrose as the D-glucopyranosyl donor to synthesize α-D-glucans of high molecular mass (>10<sup>6</sup> Da) with the concomitant release of D-fructose (Fig. 1). They are also referred to as glucosyltransferases (GTF) or glucansucrases (GS) <cite>Sidebotham1974,Monchois1999,Leemhuis2012,Andre2010</cite>. The first glucansucrase was isolated from sucrose-broth cultures of a strain of ''Ln.  mesenteroides'' <Cite>Hehre1941,Hehre1942</Cite>. The enzyme was shown to synthesize water-soluble dextran (α-1,6 linked D-glucan) from sucrose alone. Dextran from ''Ln. mesenteroides'' sp. was the first microbial polysaccharide to be commercialized and used for pharmaceutical and fine chemical applications. The glucansucrases produced by ''Streptococcus'' sp. were extensively studied on account of their major role in the formation of dental caries <Cite>Sidebotham1974,Monchois1999</Cite>.

@@ Line 29: / Line 29: @@
 == Substrate specificities ==
 [[Image:Mag Fig1.png|thumb|right|400px|'''Fig. 1. Reactions catalyzed from sucrose''']]
-GH70 enzymes are transglucosylases produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the clan GH-H.
+GH70 enzymes are [[transglycosylase|transglucosylases]] produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the [[clan]] GH-H.
 Most of the enzymes classified in this family use sucrose as the D-glucopyranosyl donor to synthesize α-D-glucans of high molecular mass (>10<sup>6</sup> Da) with the concomitant release of D-fructose (Fig. 1). They are also referred to as glucosyltransferases (GTF) or glucansucrases (GS) <cite>Sidebotham1974,Monchois1999,Leemhuis2012,Andre2010</cite>. The first glucansucrase was isolated from sucrose-broth cultures of a strain of ''Ln.  mesenteroides'' <Cite>Hehre1941,Hehre1942</Cite>. The enzyme was shown to synthesize water-soluble dextran (α-1,6 linked D-glucan) from sucrose alone. Dextran from ''Ln. mesenteroides'' sp. was the first microbial polysaccharide to be commercialized and used for pharmaceutical and fine chemical applications. The glucansucrases produced by ''Streptococcus'' sp. were extensively studied on account of their major role in the formation of dental caries <Cite>Sidebotham1974,Monchois1999</Cite>.
@@ Line 44: / Line 44: @@
 Glucansucrases also catalyze glucosyl exchange between their glucan products in "disproportionation" reactions <cite>Binderb1983</cite>. Of note, some members of GH70 produced by ''Lb. reuteri'' sp. were also reported to be able to use maltooligosaccharides as the glucosyl donor and to catalyze transfer to maltooligosaccharide acceptors via the formation of α-1,6 linkages, thus acting as 4,6-α-glucanotransferases, which suggested additional evolutionary relations between families GH70 and [[GH13]] <cite>Kralj2011,Dobruchowska2012 </cite>.
-One glucansucrase was shown to possess two catalytically active domains acting in tandem <cite>Fabre2005</Cite>. This enzyme was shown to be secreted by ''Ln. mesenteroides'' NRRLB-1299 (reclassified as ''Ln. citreum''). These domains work cooperatively to synthesize dextran with more than 20% α-1,2 branched linkages and are both classified in GH70. One domain is responsible for the synthesis of the α-1,6 linked dextran chain, whereas the second one is specific for the catalysis of α-1,2 branch formation. The truncated form of this enzyme carrying only the second catalytic domain was named α-1,2 branching sucrase as it does not catalyse sucrose polymerization and shows transglucosylase activity only in the presence of sucrose and linear α-1,6 dextran <cite>Brison2012</Cite>.
+One glucansucrase was shown to possess two catalytically-active domains acting in tandem <cite>Fabre2005</Cite>. This enzyme was shown to be secreted by ''Ln. mesenteroides'' NRRLB-1299 (reclassified as ''Ln. citreum''). These domains work cooperatively to synthesize dextran with more than 20% α-1,2 branched linkages and are both classified in GH70. One domain is responsible for the synthesis of the α-1,6 linked dextran chain, whereas the second one is specific for the catalysis of α-1,2 branch formation. The truncated form of this enzyme carrying only the second catalytic domain was named α-1,2 branching sucrase as it does not catalyse sucrose polymerization and shows transglucosylase activity only in the presence of sucrose and linear α-1,6 dextran <cite>Brison2012</Cite>.
 == Kinetics and Mechanism ==
-Enzymes from GH70 belong to the same [[clan]], GH-H, as [[GH13]] and [[GH77]] enzymes. All employ an α-retaining mechanism, in which the transfer of the glucosyl unit proceeds through the formation of a β-glucosyl ester of an aspartate side chain, which was first isolated by sequencing peptides provided by rapid quenching of enzymic reactions with labeled sucrose and extracellular glucosyltransferases from ''S. sobrinus'' <cite>Mooser1989,Mooser1991</Cite>. Once the glucosyl-enzyme intermediate is formed, the glucosyl units originating from sucrose may be transferred onto either water (hydrolysis reaction), D-fructose released from sucrose cleavage (sucrose isomer formation) or onto the growing glucan chain (main reaction) <cite>Mooser1989,Mooser1991,Moulis2006,Vujicic-Zagar2010</Cite>. When acceptors are introduced into the reaction mixture, acceptor glucosylation occurs at the expense of polymer formation, and the competition between the two reactions is controlled by acceptor recognition <cite>Koepsell1953</Cite>.  Polymer extension proceeds from the non-reducing end <cite>Moulis2006</Cite> and involves a single active site as observed in the tertiary structures of GH70 enzymes <cite>Vujicic-Zagar2010,Ito2011</Cite>.
+Enzymes from GH70 belong to the same [[clan]], GH-H, as [[GH13]] and [[GH77]] enzymes. All employ a [[retaining]] mechanism, in which the transfer of the glucosyl unit proceeds through the formation of a β-glucosyl ester of an aspartate side chain, which was first isolated by sequencing peptides provided by rapid quenching of enzymic reactions with labeled sucrose and extracellular glucosyltransferases from ''S. sobrinus'' <cite>Mooser1989,Mooser1991</Cite>. Once the β-glucosyl-enzyme intermediate is formed, the glucosyl units originating from sucrose may be transferred onto either water (hydrolysis reaction), D-fructose released from sucrose cleavage (sucrose isomer formation) or onto the growing glucan chain (main reaction) <cite>Mooser1989,Mooser1991,Moulis2006,Vujicic-Zagar2010</Cite>. When acceptors are introduced into the reaction mixture, acceptor glucosylation occurs at the expense of polymer formation, and the competition between the two reactions is controlled by acceptor recognition by the enzyme <cite>Koepsell1953</Cite>.  Polymer extension proceeds from the non-reducing end <cite>Moulis2006</Cite> and involves a single active site as observed in the tertiary structures of GH70 enzymes <cite>Vujicic-Zagar2010,Ito2011</Cite>.
 The catalytic domain of family 70 enzymes is often flanked at the N- and/or C-termini by sequences containing a series of homologous repeating units that confer glucan binding ability <cite>Monchois1999,Leemhuis2012,Janecek2000</cite>. They are found in domain V (Fig. 2) and have also been shown to influence polymer size, enzyme activity, specificity and processivity <cite>Monchois1999 Leemhuis2012 Moulis2006</cite>. However, their precise role at the molecular level is still not fully understood <cite>Vujicic-Zagar2010,Ito2011</Cite>.
 == Catalytic Residues ==
-Sequence analysis, secondary structure prediction and tertiary structure comparison with enzymes from [[GH13]] enabled the localization of a putative catalytic triad that is strictly conserved in family 70 and similar to that found in [[GH13]] <cite>Vujicic-Zagar2010 Ito2011</Cite>. This triad is formed by an aspartate (nucleophile) corresponding to the residue identified by peptide sequencing <cite>Mooser1989,Mooser1991</Cite>, a glutamate (acid/base catalyst) and a second aspartic acid that is critical for transition state stabilization <cite>Vujicic-Zagar2010,Ito2011</Cite>. The putative role of these residues in catalysis was further supported by mutations and structural analyses <cite>Monchois1999,Leemhuis2012,Andre2010</cite>.
+Sequence analysis, secondary structure prediction and tertiary structure comparison with enzymes from [[GH13]] enabled the localization of a putative catalytic triad that is strictly conserved in GH70 and similar to that found in [[GH13]] <cite>Vujicic-Zagar2010 Ito2011</Cite>. This triad is formed by an aspartate (catalytic [[nucleophile]]) corresponding to the residue identified by peptide sequencing <cite>Mooser1989,Mooser1991</Cite>, a glutamate ([[general acid/base]] catalysts) and a second aspartic acid that is critical for [[transition state]] stabilization <cite>Vujicic-Zagar2010,Ito2011</Cite>. The putative role of these residues in catalysis was further supported by mutations and structural analyses <cite>Monchois1999,Leemhuis2012,Andre2010</cite>.
 == Three-dimensional structures ==
 [[Image:GBDCD2ok.png|thumb|right|400px|'''Fig. 2. Structure scheme of a GH70 glucansucrase (by David Daude)''']]
-The 3-D structures of GTF180-DN dextransucrase from ''Lb. reuteri'' 180 <cite>Vujicic-Zagar2010</Cite>, GTF-SI from ''S. mutans'' <cite>Ito2011</Cite> and α-1,2 branching sucrase (engineered from DSR-E dextransucrase from ''Ln. citreum'' NRRL B-1299) <cite>Brison2012</Cite>, all revealed a unique fold organized as five distinct domains (Fig. 2), named C, A, B, IV and V, and made up of peptide segments that are not consecutively arranged along the peptide chain. The catalytic domain of GH70 glucansucrases consists of a (β/α)8 barrel resembling that of [[GH13]] enzymes but formed by sequences that have undergone circular permutation compared with the [[GH13]] domains <cite>Vujicic-Zagar2010,MacGregor1996</Cite>. The 3-D structures of complexes with sucrose, maltose and acarbose enabled the mapping of the active site and the identification of some determinants of GH70 enzyme product specificity.
+The 3-D structures of GTF180-DN dextransucrase from ''Lb. reuteri'' 180 <cite>Vujicic-Zagar2010</Cite>, GTF-SI from ''S. mutans'' <cite>Ito2011</Cite> and α-1,2 branching sucrase (engineered from DSR-E dextransucrase from ''Ln. citreum'' NRRL B-1299) <cite>Brison2012</Cite>, all revealed a unique fold organized as five distinct domains (Fig. 2), named C, A, B, IV and V, and made up of peptide segments that are not consecutively arranged along the peptide chain. The catalytic domain of GH70 glucansucrases consists of a (β/α)<sub>8</sub> barrel resembling that of [[GH13]] enzymes but formed by sequences that have undergone circular permutation compared with the [[GH13]] domains <cite>Vujicic-Zagar2010,MacGregor1996</Cite>. The 3-D structures of complexes with sucrose, maltose and acarbose enabled the mapping of the active site and the identification of some determinants of GH70 enzyme product specificity.
 === Available structures ===
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 == Family Firsts ==
-;First stereochemistry determination: The stereochemistry was directly linked to the discovery of the enzyme from ''Ln. mesenteroides'' catalyzing dextran synthesis from sucrose by Hehre <cite>Hehre1941</Cite>.
+;First stereochemistry determination: The [[retaining]] stereochemistry was inferred upon discovery of the enzyme from ''Ln. mesenteroides'' catalyzing dextran synthesis from sucrose by Hehre <cite>Hehre1941</Cite>.
 ;First amino acid sequences: Those of GTF-B from ''S. mutans'' and GTF-I from ''S. sobrinus'' Mfe28 simultaneously reported in two companion articles <cite>Shiroza1987,Ferretti1987</cite>.
-;First catalytic nucleophile identification: Identified first in ''S. sobrinus'' glucansucrase <cite>Mooser1989,Mooser1991</Cite>.
+;First [[catalytic nucleophile]] identification: Identified first in ''S. sobrinus'' glucansucrase <cite>Mooser1989,Mooser1991</Cite>.
-;First general acid/base residue identification: On the basis of sequence alignments and secondary structure <cite>MacGregor1996 </cite>. On the basis of 3-D-structure <cite>Vujicic-Zagar2010,Pijning2008 </Cite>.
+;First [[general acid/base]] residue identification: Assigned on the basis of sequence alignments and secondary structure <cite>MacGregor1996 </cite>. Assigned on the basis of 3-D-structure <cite>Vujicic-Zagar2010,Pijning2008 </Cite>.
 ;First 3-D structure: The first 3-D structure for GH70 members was that of the GTF180-DN dextransucrase from ''Lb. reuteri'' <cite>Vujicic-Zagar2010,Pijning2008</cite>.

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 GH70 enzymes are transglucosylases produced by lactic acid bacteria from, e.g., ''Streptococcus'', ''Leuconostoc'', ''Weisella'' or ''Lactobacillus'' genera. Together with the families [[GH13]] and [[GH77]] enzymes, they form the clan GH-H.
-Most of the enzymes classified in this family use sucrose as the D-glucopyranosyl donor to synthesize α-D-glucans of high molecular mass (>106 Da) with the concomitant release of D-fructose (Fig. 1). They are also referred to as glucosyltransferases (GTF) or glucansucrases (GS) <cite>Sidebotham1974,Monchois1999,Leemhuis2012,Andre2010</cite>. The first glucansucrase was isolated from sucrose-broth cultures of a strain of ''Ln.  mesenteroides'' <Cite>Hehre1941,Hehre1942</Cite>. The enzyme was shown to synthesize water-soluble dextran (α-1,6 linked D-glucan) from sucrose alone. Dextran from ''Ln. mesenteroides'' sp. was the first microbial polysaccharide to be commercialized and used for pharmaceutical and fine chemical applications. The glucansucrases produced by ''Streptococcus'' sp. were extensively studied on account of their major role in the formation of dental caries <Cite>Sidebotham1974,Monchois1999</Cite>.
+Most of the enzymes classified in this family use sucrose as the D-glucopyranosyl donor to synthesize α-D-glucans of high molecular mass (>10<sup>6</sup> Da) with the concomitant release of D-fructose (Fig. 1). They are also referred to as glucosyltransferases (GTF) or glucansucrases (GS) <cite>Sidebotham1974,Monchois1999,Leemhuis2012,Andre2010</cite>. The first glucansucrase was isolated from sucrose-broth cultures of a strain of ''Ln.  mesenteroides'' <Cite>Hehre1941,Hehre1942</Cite>. The enzyme was shown to synthesize water-soluble dextran (α-1,6 linked D-glucan) from sucrose alone. Dextran from ''Ln. mesenteroides'' sp. was the first microbial polysaccharide to be commercialized and used for pharmaceutical and fine chemical applications. The glucansucrases produced by ''Streptococcus'' sp. were extensively studied on account of their major role in the formation of dental caries <Cite>Sidebotham1974,Monchois1999</Cite>.
 Depending on their specificity, glucansucrases catalyze the formation of linear as well as branched α-D-glucan chains with various types of glycosidic linkages, namely α-1,2; α-1,3; α-1,4; and/or α-1,6 <cite>Sidebotham1974,Andre2010,Jeanes1954</Cite>. They are classified by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) on the basis of the reaction catalyzed and the specificity: