Glycoside Hydrolase Family 37 - Revision history

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

2021-12-18T21:17:49Z

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

Cecelia Garcia at 20:24, 13 September 2021

2021-09-13T20:24:16Z

Cecelia Garcia at 19:34, 9 September 2021

2021-09-09T19:34:43Z

Cecelia Garcia at 21:19, 8 September 2021

2021-09-08T21:19:10Z

Spencer Williams at 10:06, 13 October 2010

2010-10-13T10:06:07Z

Spencer Williams at 10:05, 13 October 2010

2010-10-13T10:05:15Z

Harry Brumer: line spacing

2010-10-09T14:59:53Z

line spacing

Harry Brumer: added EC link

2010-10-09T14:39:02Z

added EC link

Harry Brumer: standardized reference tags

2010-10-09T14:36:33Z

standardized reference tags

Gideon Davies at 20:31, 8 October 2010

2010-10-08T20:31:09Z

@@ Line 1: / Line 1: @@
 <!-- CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Tracey Gloster^^^, ^^^Cecelia Garcia^^^
+* [[Author]]: [[User:Tracey Gloster|Tracey Gloster]], [[User:Cecelia Garcia|Cecelia Garcia]]
-* [[Responsible Curator]]:  ^^^Gideon Davies^^^
+* [[Responsible Curator]]:  [[User:Gideon Davies|Gideon Davies]]
 ----

@@ Line 18: / Line 18: @@
 |-
 |'''Active site residues'''
-|Inferred
+|Known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-To date, GH37 [[glycoside hydrolases]] have been shown to hydrolyze the α-1,1 bound trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside) into two molecules of D-glucose (EC [{{EClink}}3.2.1.28 3.2.1.28]). GH37 enzymes are further classified by their optimal pH; neutral or acidic, and also by their cellular localization; soluble or membrane bound <cite>DEnfert1999</cite>.
+To date, GH37 [[glycoside hydrolases]] have been shown to hydrolyze the α-1,1 bound trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside) into two molecules of D-glucose (EC [{{EClink}}3.2.1.28 3.2.1.28]). GH37 enzymes are further classified by their optimal pH; neutral or acidic, and also by their cellular localization; soluble or membrane bound <cite>DEnfert1999</cite>. There is some evidence that organisms possessing multiple GH37 trehalases will utilize them for different purposes. This tends towards periplasmic trehalases being metabolically relevant while cytoplasmic trehalases participate in osmoregulation <cite>Arguelles2000</cite>.
 == Kinetics and Mechanism ==
@@ Line 38: / Line 38: @@
 == Catalytic Residues ==
 The catalytic residues were first predicted through structural determination of ''E. coli'' Tre37A in complex with inhibitors 1-thiatrehazolin (PDB ID [https://www.rcsb.org/structure/2JG0 2JG0]) and validoxylamine A (PDB ID [https://www.rcsb.org/structure/2JF4 2JF4]) <cite>Gibson2007</cite>. These structures implicate an aspartate residue (Asp312 in ''E. coli'') as the catalytic [[general acid/base|general acid]], and a glutamate residue (Glu496 in ''E. coli'') as the catalytic [[general acid/base|general base]]. A crystal structure of ''S. cerevisiae'' Nth1 with bound trehalose identified an aspartate residue (Asp478 in ''S. cerevisiae'') as the catalytic [[general acid/base|general acid]], and a glutamate residue (Glu674 in ''S. cerevisiae'') as the [[general acid/base|general base]]. Superimposition of these structures indicates that the proposed catalytic residues align in both the ''E. coli'' Tre37A inhibitor bound and ''S. cerevisiae'' Nth1 trehalose bound structures.
 == Three-dimensional structures ==
 The first three-dimensional structure of a GH37 trehalase was obtained from ''E. coli'' Tre37A in complex with the inhibitors 1-thiatrehazolin (PDB ID [https://www.rcsb.org/structure/2JG0 2JG0]) and validoxylamine A (PDB ID [https://www.rcsb.org/structure/2JF4 2JF4]) by x-ray crystallography <cite>Gibson2007</cite>. The structure revealed a monomeric enzyme consisting of an (α/α)6 barrel fold, similar to other α-toroidal glycosidases. The structure revealed extensive hydrogen bonding and a distinct lack of hydrophobic stacking within the +1 subsite. The bound structure also revealed that the +1 and -1 subsites were buried within the enzyme structure and significant conformation changes would be required for substrate recognition.
-The first eukaryotic GH37 structure was determined from an ''S. cerevisiae'' Nth1:Bmh1 complex, and provided the first structure in the presence of trehalose (PDB ID [https://www.rcsb.org/structure/5M4A 5M4A]) <cite>Alblova2017</cite>. The catalytic domain consists of an (α/α)6 barrel formed by the interaction of one Bmh1 C-terminus with Nth1. Similar to the ''E. coli'' Tre37A structure, the substrate was found in a deep pocket. A flexible “lid” loop structure was observed to undergo significant conformational changes and complete the active site of Nth1. A similar, but shorter, structure was revealed in ''E. coli'' Tre37A once the solved structures were superimposed <cite>Alblova2017</cite>.
+The first eukaryotic GH37 structure was determined from an ''S. cerevisiae'' Nth1:Bmh1 complex, and provided the first structure in the presence of trehalose (PDB ID [https://www.rcsb.org/structure/5M4A 5M4A]) <cite>Alblova2017</cite>. The catalytic domain consists of an (α/α)6 barrel formed by the interaction of one Bmh1 C-terminus with Nth1. Similar to the ''E. coli'' Tre37A structure, the substrate was found in a deep pocket. This structure provided the first evidence of a flexible “lid loop” structure, which would undergo significant conformational changes and complete the active site of Nth1. A similar, but shorter, structure was revealed in ''E. coli'' Tre37A once the solved structures were superimposed <cite>Alblova2017</cite>.
 GH37 enzymes belong to the [[clans|clan]] GH-G.
@@ Line 48: / Line 52: @@
 == Family Firsts ==
 ;First sterochemistry determination: The inversion of stereochemistry for a trehalase from the flesh fly ''Sarcophaga barbata'' was first demonstrated by Clifford in 1980 <cite>Clifford1980</cite>.
-;First [[general acid]] identification: First predicted in E. coli Tre37A from structure determination with inhibitors <cite>Gibson2007</cite>, observed in structural determination of S. cerevisiae complexed with trehalose <cite>Alblova2017</cite>.
+;First [[general acid]] identification: First predicted in ''E. coli'' Tre37A from structure determination with inhibitors <cite>Gibson2007</cite>, experimentally observed in ''S. frugiperda'' through site-directed mutagenesis and kinetic determination <cite>Silva2010</cite>.
-;First [[general base]] identification: First predicted in E. coli Tre37A from structure determination with inhibitors <cite>Gibson2007</cite>, observed in structural determination of S. cerevisiae complexed with trehalose <cite>Alblova2017</cite>.
+;First [[general base]] identification: First predicted in ''E. coli'' Tre37A from structure determination with inhibitors <cite>Gibson2007</cite>, experimentally observed in ''S. frugiperda'' through site-directed mutagenesis and kinetic determination <cite>Silva2010</cite>.
 ;First 3-D structure: The GH37 trehalase from ''Escherichia coli'' was solved by X-ray crystallography <cite>Gibson2007</cite>.
@@ Line 55: / Line 59: @@
 <biblio>
 #DEnfert1999 pmid=10320571
 #Clifford1980 pmid=7341233
 #Gibson2007 pmid=17455176
 #Alblova2017 pmid=29087344
 #Alblova2019 pmid=30628830

@@ Line 37: / Line 37: @@
 == Catalytic Residues ==
-The catalytic residues have not been demonstrated unequivocally, but structural determination of the trehalase from ''Escherichia coli'' in complex with inhibitors in the active site implicate an aspartate residue (Asp312 in ''E. coli'') as the catalytic [[general acid]] and a glutamate residue (Glu496 in ''E. coli'') as the catalytic [[general base]] <cite>Gibson2007</cite>.
+The catalytic residues were first predicted through structural determination of ''E. coli'' Tre37A in complex with inhibitors 1-thiatrehazolin (PDB ID [https://www.rcsb.org/structure/2JG0 2JG0]) and validoxylamine A (PDB ID [https://www.rcsb.org/structure/2JF4 2JF4]) <cite>Gibson2007</cite>. These structures implicate an aspartate residue (Asp312 in ''E. coli'') as the catalytic [[general acid/base|general acid]], and a glutamate residue (Glu496 in ''E. coli'') as the catalytic [[general acid/base|general base]]. A crystal structure of ''S. cerevisiae'' Nth1 with bound trehalose identified an aspartate residue (Asp478 in ''S. cerevisiae'') as the catalytic [[general acid/base|general acid]], and a glutamate residue (Glu674 in ''S. cerevisiae'') as the [[general acid/base|general base]]. Superimposition of these structures indicates that the proposed catalytic residues align in both the ''E. coli'' Tre37A inhibitor bound and ''S. cerevisiae'' Nth1 trehalose bound structures.
 == Three-dimensional structures ==
-The only structural representative from GH37 to date is the trehalase from ''Escherichia coli'', which was solved using X-ray crystallography <cite>Gibson2007</cite>. The structure revealed a (α/α)<sub>6</sub> barrel fold, similar to other α-toroidal glycosidases such as those in families [[GH94]], [[GH15]] and [[GH65]].  GH37 falls into [[clans|clan]] GH-G. Structures have been solved with the inhibitors validoxylamine A, 1-thiatrehazolin and casuarine analogues <cite>Gibson2007,Cardona2009,Cardona2010</cite>.
+The first three-dimensional structure of a GH37 trehalase was obtained from ''E. coli'' Tre37A in complex with the inhibitors 1-thiatrehazolin (PDB ID [https://www.rcsb.org/structure/2JG0 2JG0]) and validoxylamine A (PDB ID [https://www.rcsb.org/structure/2JF4 2JF4]) by x-ray crystallography <cite>Gibson2007</cite>. The structure revealed a monomeric enzyme consisting of an (α/α)6 barrel fold, similar to other α-toroidal glycosidases. The structure revealed extensive hydrogen bonding and a distinct lack of hydrophobic stacking within the +1 subsite. The bound structure also revealed that the +1 and -1 subsites were buried within the enzyme structure and significant conformation changes would be required for substrate recognition.
 == Family Firsts ==
 ;First sterochemistry determination: The inversion of stereochemistry for a trehalase from the flesh fly ''Sarcophaga barbata'' was first demonstrated by Clifford in 1980 <cite>Clifford1980</cite>.
-;First [[general acid]] identification: Predicted from structure determination <cite>Gibson2007</cite>, but not shown unequivocally.
+;First [[general acid]] identification: First predicted in E. coli Tre37A from structure determination with inhibitors <cite>Gibson2007</cite>, observed in structural determination of S. cerevisiae complexed with trehalose <cite>Alblova2017</cite>.
-;First [[general base]] identification: Predicted from structure determination <cite>Gibson2007</cite>, but not shown unequivocally.
+;First [[general base]] identification: First predicted in E. coli Tre37A from structure determination with inhibitors <cite>Gibson2007</cite>, observed in structural determination of S. cerevisiae complexed with trehalose <cite>Alblova2017</cite>.
 ;First 3-D structure: The GH37 trehalase from ''Escherichia coli'' was solved by X-ray crystallography <cite>Gibson2007</cite>.
@@ Line 55: / Line 59: @@
 #Alblova2017 pmid=29087344
 #Alblova2019 pmid=30628830

@@ Line 1: / Line 1: @@
 <!-- CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Tracey Gloster^^^
+* [[Author]]: ^^^Tracey Gloster^^^, ^^^Cecelia Garcia^^^
 * [[Responsible Curator]]:  ^^^Gideon Davies^^^
 ----
@@ Line 29: / Line 29: @@
 == Substrate specificities ==
-GH37 [[glycoside hydrolases]] have been shown, to date, to hydrolyse only the disaccharide trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside) into two molecules of D-glucose (EC [{{EClink}}3.2.1.28 3.2.1.28]).
+To date, GH37 [[glycoside hydrolases]] have been shown to hydrolyze the α-1,1 bound trehalose (α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside) into two molecules of D-glucose (EC [{{EClink}}3.2.1.28 3.2.1.28]). GH37 enzymes are further classified by their optimal pH; neutral or acidic, and also by their cellular localization; soluble or membrane bound <cite>DEnfert1999</cite>.
 == Kinetics and Mechanism ==
-A trehalase from flesh fly was shown to hydrolyse with [[inverting|inversion]] of anomeric stereochemistry using <sup>18</sup>O-labelled water <cite>Clifford1980</cite>. The structural solution of the trehalase from ''Escherichia coli'' also demonstrates the active site catalytic residues are in a position consistent with an [[inverting]] mechanism <cite>Gibson2007</cite>.
+GH37 trehalases follow an [[inverting]] mechanism. This was first demonstrated through incubation of GH37 trehalases obtained from ''S. barbata'', the flesh fly, with <sup>18</sup>O-labelled water and observing its incorporation primarily into the beta-epimer <cite>Clifford1980</cite>. This was further supported by the solved structure of ''E. coli'' Tre37A which demonstrated that the proposed catalytic residues were in a position consistent with an [[inverting]] mechanism <cite>Gibson2007</cite>.
 == Catalytic Residues ==
@@ Line 48: / Line 50: @@
 == References ==
 <biblio>
 #Clifford1980 pmid=7341233
 #Gibson2007 pmid=17455176
 #Cardona2009 pmid=19123216
 #Cardona2010 pmid=20461849

@@ Line 38: / Line 38: @@
 == Three-dimensional structures ==
-The only structural representative from GH37 to date is the trehalase from ''Escherichia coli'', which was solved using X-ray crystallography <cite>Gibson2007</cite>. The structure revealed a (α/α)<sub>6</sub> barrel fold, similar to other α-toroidal glycosidases such as those in families [[GH94]], [[GH15]] and [[GH65]].  GH37 falls into [[clan]] GH-G. Structures have been solved with the inhibitors validoxylamine A, 1-thiatrehazolin and casuarine analogues <cite>Gibson2007,Cardona2009,Cardona2010</cite>.
+The only structural representative from GH37 to date is the trehalase from ''Escherichia coli'', which was solved using X-ray crystallography <cite>Gibson2007</cite>. The structure revealed a (α/α)<sub>6</sub> barrel fold, similar to other α-toroidal glycosidases such as those in families [[GH94]], [[GH15]] and [[GH65]].  GH37 falls into [[clans|clan]] GH-G. Structures have been solved with the inhibitors validoxylamine A, 1-thiatrehazolin and casuarine analogues <cite>Gibson2007,Cardona2009,Cardona2010</cite>.
 == Family Firsts ==

@@ Line 22: / Line 22: @@
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
 |-
-| colspan="2" |http://www.cazy.org/fam/GH37.html
+| colspan="2" |{{CAZyDBlink}}GH37.html
 |}
 </div>
@@ Line 32: / Line 32: @@
 == Kinetics and Mechanism ==
-A trehalase from flesh fly was shown to hydrolyse with inversion of stereochemistry using <sup>18</sup>O labelled water <cite>REF1</cite>. The structural solution of the trehalase from ''Escherichia coli'' also demonstrates the active site catalytic residues are in a position consistent with an [[inverting mechanism]] <cite>REF2</cite>.
+A trehalase from flesh fly was shown to hydrolyse with inversion of stereochemistry using <sup>18</sup>O labelled water <cite>Clifford1980</cite>. The structural solution of the trehalase from ''Escherichia coli'' also demonstrates the active site catalytic residues are in a position consistent with an [[inverting mechanism]] <cite>Gibson2007</cite>.
 == Catalytic Residues ==
-The catalytic residues have not been demonstrated unequivocally, but structural determination of the trehalase from ''Escherichia coli'' in complex with inhibitors in the active site implicate an aspartate residue (Asp312 in ''E. coli'') as the catalytic acid and a glutamate residue (Glu496 in ''E. coli'') as the catalytic base <cite>REF2</cite>.
+The catalytic residues have not been demonstrated unequivocally, but structural determination of the trehalase from ''Escherichia coli'' in complex with inhibitors in the active site implicate an aspartate residue (Asp312 in ''E. coli'') as the catalytic acid and a glutamate residue (Glu496 in ''E. coli'') as the catalytic base <cite>Gibson2007</cite>.
 == Three-dimensional structures ==
-The only structural representative from GH37 to date is the trehalase from ''Escherichia coli'', which was solved using X-ray crystallography <cite>REF2</cite>. The structure revealed a (α/α)<sub>6</sub> barrel fold, similar to other α-toroidal glycosidases such as those in families [[GH94]], [[GH15]] and [[GH65]].  GH37 falls into clan GH-G. Structures have been solved with the inhibitors validoxylamine A, 1-thiatrehazolin and casuarine analogues <cite>REF2,REF3,REF4</cite>.
+The only structural representative from GH37 to date is the trehalase from ''Escherichia coli'', which was solved using X-ray crystallography <cite>Gibson2007</cite>. The structure revealed a (α/α)<sub>6</sub> barrel fold, similar to other α-toroidal glycosidases such as those in families [[GH94]], [[GH15]] and [[GH65]].  GH37 falls into clan GH-G. Structures have been solved with the inhibitors validoxylamine A, 1-thiatrehazolin and casuarine analogues <cite>Gibson2007,Cardona2009,Cardona2010</cite>.
 == Family Firsts ==
-;First sterochemistry determination: The inversion of stereochemistry for a trehalase from the flesh fly ''Sarcophaga barbata'' was first demonstrated by Clifford in 1980 <cite>REF1</cite>.
+;First sterochemistry determination: The inversion of stereochemistry for a trehalase from the flesh fly ''Sarcophaga barbata'' was first demonstrated by Clifford in 1980 <cite>Clifford1980</cite>.
-;First catalytic nucleophile identification: Predicted from structure determination <cite>REF2</cite>, but not shown unequivocally.
+;First catalytic nucleophile identification: Predicted from structure determination <cite>Gibson2007</cite>, but not shown unequivocally.
-;First general acid/base residue identification: Predicted from structure determination <cite>REF2</cite>, but not shown unequivocally.
+;First general acid/base residue identification: Predicted from structure determination <cite>Gibson2007</cite>, but not shown unequivocally.
-;First 3-D structure: The GH37 trehalase from ''Escherichia coli'' was solved by X-ray crystallography <cite>REF2</cite>.
+;First 3-D structure: The GH37 trehalase from ''Escherichia coli'' was solved by X-ray crystallography <cite>Gibson2007</cite>.
 == References ==
 <biblio>
-#REF1 pmid=7341233
+#Clifford1980 pmid=7341233
-#REF2 pmid=17455176
+#Gibson2007 pmid=17455176
-#REF3 pmid=19123216
+#Cardona2009 pmid=19123216
-#REF4 pmid=20461849
+#Cardona2010 pmid=20461849