Carbohydrate Binding Module Family 46 - Revision history

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

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Harry Brumer: /* Family Firsts */

2018-01-31T19:01:31Z

Family Firsts

Elizabeth Ficko-Blean at 08:57, 31 January 2018

2018-01-31T08:57:49Z

Elizabeth Ficko-Blean at 08:50, 31 January 2018

2018-01-31T08:50:18Z

Elizabeth Ficko-Blean at 08:48, 31 January 2018

2018-01-31T08:48:01Z

Harry Gilbert at 18:30, 30 January 2018

2018-01-30T18:30:38Z

Harry Gilbert at 18:30, 30 January 2018

2018-01-30T18:30:01Z

Harry Gilbert at 18:07, 30 January 2018

2018-01-30T18:07:53Z

Harry Gilbert at 18:05, 30 January 2018

2018-01-30T18:05:11Z

Elizabeth Ficko-Blean: Created page with " {{UnderConstruc..."

2018-01-24T10:34:33Z

Created page with "  {{UnderConstruc..."

New page

{{UnderConstruction}}
* [[Author]]: ^^^Harry Gilbert^^^
* [[Responsible Curator]]: ^^^Elizabeth Ficko-Blean^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CBM46.html
|}
</div>


== Ligand specificities ==
Mention here all major natural ligand specificities that are found within a given family (also plant or mammalian origin). Certain linkages and promiscuity would also be mentioned here if biologically relevant.

''Note: Here is an example of how to insert references in the text, together with the "biblio" section below:'' Please see these references for an essential introduction to the CAZy classification system: <cite>DaviesSinnott2008 Cantarel2009</cite>. CBMs, in particular, have been extensively reviewed <cite>Boraston2004 Hashimoto2006 Shoseyov2006 Guillen2010</cite>.

== 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
:Insert archetype here, possibly including ''very brief'' synopsis.
;First Structural Characterization
:Insert archetype here, possibly including ''very brief'' synopsis.

== References ==
<biblio>
#Cantarel2009 pmid=18838391
#DaviesSinnott2008 Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. ''The Biochemist'', vol. 30, no. 4., pp. 26-32. [http://www.biochemist.org/bio/03004/0026/030040026.pdf Download PDF version].
#Boraston2004 pmid=15214846
#Hashimoto2006 pmid=17131061
#Shoseyov2006 pmid=16760304
#Guillen2010 pmid=19908036
</biblio>

[[Category:Carbohydrate Binding Module Families|CBM046]]

@@ Line 20: / Line 20: @@
 CBM46  is a Gram-positive bacterial CBM family that comprises around 110 amino acids. The one member of this family characterized to date did not bind to soluble or insoluble polysaccharides as a discrete entity <cite>Wamalwa2006,Venditto2015</cite>. In the context of the full length enzyme, BhCel5B, the CBM46 (BhCBM46) made a significant contribution to binding xyloglucan and &beta;1,3-&beta;1,4-mixed linked glucans. Thus, an inactive form of the catalytic module of BhCel5B (lacks the catalytic nucleophile) did not bind to &beta;1,3-&beta;1,4-mixed linked glucan and had a ''K''<sub>A</sub> for xyloglucan of 10<sup>4</sup> M<sup>-1</sup> , while the inactive full length enzyme (containing both the GH5 catalytic module and the CBM46) had affinities for the two glucans of 10<sup>5</sup> M<sup>-1</sup>and 5 x 10<sup>7</sup> M<sup>-1</sup>, respectively.
 == Structural Features ==
-[[File:CBM46fold.png|thumb|300px|right|'''Figure 1.'''  The fold of BhCel5B from ''B. halodurans'' Xyn10A (see [{{PDBlink}}4v2x PDB ID 4v2x]) highlighting the three modules of the enzyme comprising the N-terminal GH5 catalytic module (blue), internal immunoglobulin domain (green) and the C-terminal CBM46]]The crystal structure of BhCBM46 as a discrete entity and in the full length enzyme (''Bacillus halodurans'' GH5 glucanase BhCel5B) was determined. The CBM displays a classic β-sandwich jelly roll fold (Figure 1) <cite>Venditto2015</cite>. The two β-sheets each contain four anti-parallel β-strands. The order of the β-strands in β-sheet 1 and β-sheet 2 are β1, β2, β5, β4 and β3, β6, β7, β8, respectively. A loop connecting the two &beta;sheets, by linking β-strands 3 and 4, provides an extended planar/slightly curved surface containing five aromatic residues. Mutagenesis and conservation of some of these residues suggests that the loop comprises the ligand binding site in BhCBM46, but only in the context of the full length enzyme shown in '''Figure 1''' (see [{{PDBlink}}4v2x PDB ID 4v2x]) <cite>Venditto2015</cite>.
+[[File:CBM46fold.png|thumb|300px|right|'''Figure 1.'''  The fold of BhCel5B from ''B. halodurans'' Xyn10A (see [{{PDBlink}}4v2x PDB ID 4v2x]) highlighting the three modules of the enzyme comprising the N-terminal GH5 catalytic module (blue), internal immunoglobulin domain (green) and the C-terminal CBM46]]The crystal structure of BhCBM46 as a discrete entity and in the full length enzyme (''Bacillus halodurans'' GH5 glucanase BhCel5B) was determined. The CBM displays a classic β-sandwich jelly roll fold (Figure 1) <cite>Venditto2015</cite>. The two β-sheets each contain four anti-parallel β-strands. The order of the β-strands in β-sheet 1 and β-sheet 2 are β1, β2, β5, β4 and β3, β6, β7, β8, respectively. A loop connecting the two &beta;-sheets, by linking β-strands 3 and 4, provides an extended planar/slightly curved surface containing five aromatic residues. Mutagenesis and conservation of some of these residues suggests that the loop comprises the ligand binding site in BhCBM46, but only in the context of the full length enzyme shown in '''Figure 1''' (see [{{PDBlink}}4v2x PDB ID 4v2x]) <cite>Venditto2015</cite>.
 == Functionalities ==
 All CBM46s are located at the C-terminus of enzymes that contain an N-terminal GH5_4 catalytic module and a central immunoglobulin domain <cite>Wamalwa2006,Venditto2015</cite>. Deleting BhCBM46 from BhCel5B reduced the activity of the enzyme against &beta;1,3-&beta;1,4-mixed linked glucans by ~80-fold, and it was proposed that the kink in the glucan caused by the &beta;1,3-linkage enabled a single chain to interact with both the catalytic module and CBM46 <cite>Venditto2015</cite>. The inability of a CBM to bind its ligand in isolation but contribute to directing substrate into the active site of the enzyme is similar to the role of [[CBM3]]c in some [[GH9]] processive cellulases <cite>Sakon1997</cite>. The truncated BhCel5B enzyme displayed similar activity to the wild type enzyme against soluble xyloglucan indicating that the linear trajectory of β-1,4-glucan chains would prevent these polymers from occupying both the substrate binding cleft and CBM binding surface. In contrast, BhCBM46 had a substantial impact on the capacity of BhCel5B to hydrolyse the xyloglucan in plant cell walls. It was proposed that the CBM, in conjunction with a region of the catalytic module that is distinct from the active site/substrate binding cleft, tethers the enzyme to regions rich in xyloglucan. This enables the substrate binding cleft to readily access xyloglucan chains that are not interacting with the CBM <cite>Venditto2015</cite>.

@@ Line 18: / Line 18: @@
 == Ligand specificities ==
-CBM46  is a Gram-positive bacterial family that comprise around 110 amino acids. The one member of this family characterized to date did not bind to soluble or insoluble polysaccharides as a discrete entity <cite>Wamalwa2006,Venditto2015</cite>. In the context of the full length enzyme, BhCel5B, the CBM46 (BhCBM46) made a significant contribution to binding xyloglucan and &beta;1,3-&beta;1,4-mixed linked glucans. Thus, an inactive form of the catalytic module of BhCel5B (lacks the catalytic nucleophile) did not bind to &beta;1,3-&beta;1,4-mixed linked glucan and had a K<sub>A</sub> for xyloglucan of 10<sup>4</sup> M<sup>-1</sup> , while the inactive full length enzyme (containing both the GH5 catalytic module and the CBM46) had affinities for the two glucans of 10<sup>5</sup> M<sup>-1</sup>and 5 x 10<sup>7</sup> M<sup>-1</sup>, respectively.
+CBM46  is a Gram-positive bacterial CBM family that comprises around 110 amino acids. The one member of this family characterized to date did not bind to soluble or insoluble polysaccharides as a discrete entity <cite>Wamalwa2006,Venditto2015</cite>. In the context of the full length enzyme, BhCel5B, the CBM46 (BhCBM46) made a significant contribution to binding xyloglucan and &beta;1,3-&beta;1,4-mixed linked glucans. Thus, an inactive form of the catalytic module of BhCel5B (lacks the catalytic nucleophile) did not bind to &beta;1,3-&beta;1,4-mixed linked glucan and had a ''K''<sub>A</sub> for xyloglucan of 10<sup>4</sup> M<sup>-1</sup> , while the inactive full length enzyme (containing both the GH5 catalytic module and the CBM46) had affinities for the two glucans of 10<sup>5</sup> M<sup>-1</sup>and 5 x 10<sup>7</sup> M<sup>-1</sup>, respectively.
 == Structural Features ==
-[[File:CBM46fold.png|thumb|300px|right|'''Figure 1.'''  The fold of BhCel5B from ''B. halodurans'' Xyn10A (see [{{PDBlink}}4v2x PDB ID 4v2x]) highlighting the three modules of the enzyme comprising the N-terminal GH5 catalytic module (blue), internal immunoglobulin domain (green) and the C-terminal CBM46]]The crystal structure of BhCBM46 as a discrete entity and in the full length enzyme (''Bacillus halodurans'' GH5 glucanase BhCel5B) was determined. The CBM displays a classic β-sandwich jelly roll fold (Figure 1) <cite>Venditto2015</cite>. The two β-sheets each contain four anti-parallel β-strands. The order of the β-strands in β-sheet 1 and β-sheet 2 are β1, β2, β5, β4 and β3, β6, β7, β8, respectively. A loop connecting the two &beta;sheets, by linking β-strand 3 and 4, provides an extended planar/slightly curved surface containing five aromatic residues. Mutagenesis and conservation of some of these residues suggests that the loop comprises the ligand binding site in BhCBM46, but only in the context of the full length enzyme shown in '''Figure 1''' (see [{{PDBlink}}4v2x PDB ID 4v2x]) <cite>Venditto2015</cite>.
+[[File:CBM46fold.png|thumb|300px|right|'''Figure 1.'''  The fold of BhCel5B from ''B. halodurans'' Xyn10A (see [{{PDBlink}}4v2x PDB ID 4v2x]) highlighting the three modules of the enzyme comprising the N-terminal GH5 catalytic module (blue), internal immunoglobulin domain (green) and the C-terminal CBM46]]The crystal structure of BhCBM46 as a discrete entity and in the full length enzyme (''Bacillus halodurans'' GH5 glucanase BhCel5B) was determined. The CBM displays a classic β-sandwich jelly roll fold (Figure 1) <cite>Venditto2015</cite>. The two β-sheets each contain four anti-parallel β-strands. The order of the β-strands in β-sheet 1 and β-sheet 2 are β1, β2, β5, β4 and β3, β6, β7, β8, respectively. A loop connecting the two &beta;sheets, by linking β-strands 3 and 4, provides an extended planar/slightly curved surface containing five aromatic residues. Mutagenesis and conservation of some of these residues suggests that the loop comprises the ligand binding site in BhCBM46, but only in the context of the full length enzyme shown in '''Figure 1''' (see [{{PDBlink}}4v2x PDB ID 4v2x]) <cite>Venditto2015</cite>.
 == Functionalities ==
-All CBM46s are located at the C-terminus of enzymes that contain an N-terminal GH5_4 catalytic module and a central immunoglobulin domain <cite>Wamalwa2006,Venditto2015</cite>. Deleting BhCBM46 from BhCel5B reduced the activity of the enzyme against &beta;1,3-&beta;1,4-mixed linked glucans by ~80-fold, and it was proposed that the kink in the glucan caused by the &beta;1,3-linkage enabled a single chain to interact with both the catalytic module and CBM46 <cite>Venditto2015</cite>. The inability of a CBM to bind its ligand in isolation but contribute to directing substrate into the active site of the enzyme is similar to the role of CBM3c in some GH9 processive cellulases <cite>Sakon1997</cite>. In contrast the same truncated enzyme displayed similar activity to the wild type enzyme against soluble xyloglucan indicating that the linear trajectory of β-1,4-glucan chains would prevent these polymers from occupying both the substrate binding cleft and CBM binding surface. In contrast BhCBM46 had a substantial impact on the capacity of BhCel5B to hydrolyse the xyloglucan in plant cell walls. It was proposed that the CBM, in conjunction with a region of the catalytic module that is distinct from the active site/substrate binding cleft, tethers the enzyme to regions rich in xyloglucan. This enables the substrate binding cleft to readily access xyloglucan chains that are not interacting with the CBM <cite>Venditto2015</cite>.
+All CBM46s are located at the C-terminus of enzymes that contain an N-terminal GH5_4 catalytic module and a central immunoglobulin domain <cite>Wamalwa2006,Venditto2015</cite>. Deleting BhCBM46 from BhCel5B reduced the activity of the enzyme against &beta;1,3-&beta;1,4-mixed linked glucans by ~80-fold, and it was proposed that the kink in the glucan caused by the &beta;1,3-linkage enabled a single chain to interact with both the catalytic module and CBM46 <cite>Venditto2015</cite>. The inability of a CBM to bind its ligand in isolation but contribute to directing substrate into the active site of the enzyme is similar to the role of [[CBM3]]c in some [[GH9]] processive cellulases <cite>Sakon1997</cite>. The truncated BhCel5B enzyme displayed similar activity to the wild type enzyme against soluble xyloglucan indicating that the linear trajectory of β-1,4-glucan chains would prevent these polymers from occupying both the substrate binding cleft and CBM binding surface. In contrast, BhCBM46 had a substantial impact on the capacity of BhCel5B to hydrolyse the xyloglucan in plant cell walls. It was proposed that the CBM, in conjunction with a region of the catalytic module that is distinct from the active site/substrate binding cleft, tethers the enzyme to regions rich in xyloglucan. This enables the substrate binding cleft to readily access xyloglucan chains that are not interacting with the CBM <cite>Venditto2015</cite>.
 == Family Firsts ==
 ;First Identified

@@ Line 25: / Line 25: @@
 == Family Firsts ==
 ;First Identified
-The first CBM46 to be identified (BhCBM46) was from ''B. halodurans'' Cel5B <cite>Wamalwa2006,Venditto2015</cite>
+The first CBM46 to be identified (BhCBM46) was from ''B. halodurans'' Cel5B <cite>Wamalwa2006</cite>
 ;First Structural Characterization
 The first crystal structure of a CBM46 was BhCBM46 <cite>Venditto2015</cite>.

@@ Line 20: / Line 20: @@
 CBM46  is a Gram-positive bacterial family that comprise around 110 amino acids. The one member of this family characterized to date did not bind to soluble or insoluble polysaccharides as a discrete entity <cite>Wamalwa2006,Venditto2015</cite>. In the context of the full length enzyme, BhCel5B, the CBM46 (BhCBM46) made a significant contribution to binding xyloglucan and &beta;1,3-&beta;1,4-mixed linked glucans. Thus, an inactive form of the catalytic module of BhCel5B (lacks the catalytic nucleophile) did not bind to &beta;1,3-&beta;1,4-mixed linked glucan and had a K<sub>A</sub> for xyloglucan of 10<sup>4</sup> M<sup>-1</sup> , while the inactive full length enzyme (containing both the GH5 catalytic module and the CBM46) had affinities for the two glucans of 10<sup>5</sup> M<sup>-1</sup>and 5 x 10<sup>7</sup> M<sup>-1</sup>, respectively.
 == Structural Features ==
-The crystal structure of BhCBM46 as a discrete entity and in the full length enzyme (''Bacillus halodurans'' GH5 glucanase BhCel5B) was determined. The CBM displays a classic β-sandwich jelly roll fold. The two β-sheets each contain four anti-parallel β-strands. The order of the β-strands in β-sheet 1 and β-sheet 2 are β1, β2, β5, β4 and β3, β6, β7, β8, respectively. A loop connecting the two &beta;sheets, by linking β-strand 3 and 4, provides an extended planar/slightly curved surface containing five aromatic residues. Mutagenesis and conservation of some of these residues suggests that the loop comprises the ligand binding site in BhCBM46, but only in the context of the full length enzyme <cite>Venditto2015</cite>.
+[[File:CBM46fold.png|thumb|300px|right|'''Figure 1.'''  The fold of BhCel5B from ''B. halodurans'' Xyn10A (see [{{PDBlink}}4v2x PDB ID 4v2x]) highlighting the three modules of the enzyme comprising the N-terminal GH5 catalytic module (blue), internal immunoglobulin domain (green) and the C-terminal CBM46]]The crystal structure of BhCBM46 as a discrete entity and in the full length enzyme (''Bacillus halodurans'' GH5 glucanase BhCel5B) was determined. The CBM displays a classic β-sandwich jelly roll fold (Figure 1) <cite>Venditto2015</cite>. The two β-sheets each contain four anti-parallel β-strands. The order of the β-strands in β-sheet 1 and β-sheet 2 are β1, β2, β5, β4 and β3, β6, β7, β8, respectively. A loop connecting the two &beta;sheets, by linking β-strand 3 and 4, provides an extended planar/slightly curved surface containing five aromatic residues. Mutagenesis and conservation of some of these residues suggests that the loop comprises the ligand binding site in BhCBM46, but only in the context of the full length enzyme shown in '''Figure 1''' (see [{{PDBlink}}4v2x PDB ID 4v2x]) <cite>Venditto2015</cite>.
 == Functionalities ==
 All CBM46s are located at the C-terminus of enzymes that contain an N-terminal GH5_4 catalytic module and a central immunoglobulin domain <cite>Wamalwa2006,Venditto2015</cite>. Deleting BhCBM46 from BhCel5B reduced the activity of the enzyme against &beta;1,3-&beta;1,4-mixed linked glucans by ~80-fold, and it was proposed that the kink in the glucan caused by the &beta;1,3-linkage enabled a single chain to interact with both the catalytic module and CBM46 <cite>Venditto2015</cite>. The inability of a CBM to bind its ligand in isolation but contribute to directing substrate into the active site of the enzyme is similar to the role of CBM3c in some GH9 processive cellulases <cite>Sakon1997</cite>. In contrast the same truncated enzyme displayed similar activity to the wild type enzyme against soluble xyloglucan indicating that the linear trajectory of β-1,4-glucan chains would prevent these polymers from occupying both the substrate binding cleft and CBM binding surface. In contrast BhCBM46 had a substantial impact on the capacity of BhCel5B to hydrolyse the xyloglucan in plant cell walls. It was proposed that the CBM, in conjunction with a region of the catalytic module that is distinct from the active site/substrate binding cleft, tethers the enzyme to regions rich in xyloglucan. This enables the substrate binding cleft to readily access xyloglucan chains that are not interacting with the CBM <cite>Venditto2015</cite>.

@@ Line 30: / Line 30: @@
 == References ==
 <biblio>
-#Wamalwa2006 pmid=18838391
+#Wamalwa2006 pmid=16950908
-#Venditto2015 pmid=15214846
+#Venditto2015 pmid=25713075
-#Sakon1997 pmid=17131061
+#Sakon1997 pmid=9334746
 </biblio>
 [[Category:Carbohydrate Binding Module Families|CBM046]] <!-- ATTENTION: Make sure to replace "nnn" with a three digit family number, e.g. "032" or "105" etc., for proper sorting of the page by family number. -->

@@ Line 2: / Line 2: @@
 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Harry Gilbert^^^
+* [[Author]]: [[User:Harry Gilbert|Harry Gilbert]]
-* [[Responsible Curator]]:  ^^^Elizabeth Ficko-Blean^^^
+* [[Responsible Curator]]:  [[User:Elizabeth Ficko-Blean|Elizabeth Ficko-Blean]]
 ----