Difference between revisions of "Carbohydrate Binding Module Family 70"

Revision as of 18:33, 29 October 2024

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CAZy DB link
https://www.cazy.org/CBM70.html

Ligand specificities

The CBM70 family comprises members predominantly of bacterial origin. Notably, it is the only known family with a specific binding affinity for hyaluronic acid, a linear glycosaminoglycan composed of repeating disaccharide units of β-1,4-ᴅ-glucuronic acid-β-1,3-N-acetyl-ᴅ-glucosamine. Studies have shown that CBM70 modules typically do not bind to other glycosaminoglycans, such as chondroitin sulfate, dermatan sulfate, or heparin [1, 2].

Structural Features

CBM70 modules are typically composed of approximately 160 amino acids. The crystal structure of the N-terminal CBM70 module (SpCBM70) from S. pneumoniae hyaluronate lyase Hyl has been determined. SpCBM70 adopts a classic β-jelly roll fold, consisting of two opposing 5-stranded antiparallel β-sheets. This slightly bowed sandwich structure creates a groove along the concave surface, which carries a significant positive charge and is highly conserved within the CBM70 family [1].

Figure 1. The fold of the hyaluronic acid binding molecule SpCBM70 from the Streptococcus pneumoniae hyaluronate lyase Hyl (PDB ID: 4D0Q). The structure is rotated 90 degrees to illustrate the overall fold and the arrangement of β-sheet.

Functionalities

CBM70 domains are commonly found as accessory modules in hyaluronate lyases produced by bacteria of the Streptococcus genus. These domains enhance the enzyme capability to degrade hyaluronic acid, a crucial component of the host's extracellular matrix. During infection, pathogens such as S. pneumoniae utilize hyaluronate lyase to break down hyaluronic acid, facilitating bacterial invasion and spread. CBM70 domains boost this process by increasing the binding efficiency of the enzyme, playing a key role in pathogen virulence and contributing to the high specificity of the enzyme for hyaluronic acid. Additionally, CBM70 domains have been effectively utilized in lateral flow immunoassays for the specific detection of hyaluronic acid, demonstrating their potential in diagnostic applications [2].

Family Firsts

First Identified

The first CBM70 module to be identified (SpCBM70) was from the S. pneumoniae hyaluronate lyase Hyl.

First Structural Characterization

The first crystal structure of a CBM70 module was also that of SpCBM70, PDB ID 4D0Q.

References

All Medline abstracts: PubMed

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 == 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.
+The CBM70 family comprises members predominantly of bacterial origin. Notably, it is the only known family with a specific binding affinity for hyaluronic acid, a linear glycosaminoglycan composed of repeating disaccharide units of β-1,4-ᴅ-glucuronic acid-β-1,3-N-acetyl-ᴅ-glucosamine. Studies have shown that CBM70 modules typically do not bind to other glycosaminoglycans, such as chondroitin sulfate, dermatan sulfate, or heparin <cite>Michael2014 Xuanwei2022</cite>.
-''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 Armenta2017</cite>.
 == Structural Features ==
-''Content in this section should include, in paragraph form, a description of:''
+CBM70 modules are typically composed of approximately 160 amino acids. The crystal structure of the N-terminal CBM70 module (SpCBM70) from ''S. pneumoniae'' hyaluronate lyase Hyl has been determined. SpCBM70 adopts a classic β-jelly roll fold, consisting of two opposing 5-stranded antiparallel β-sheets. This slightly bowed sandwich structure creates a groove along the concave surface, which carries a significant positive charge and is highly conserved within the CBM70 family <cite>Michael2014</cite>.[[File:CBM70.png|thumb|'''Figure 1.''' The fold of the hyaluronic acid binding molecule SpCBM70 from the ''Streptococcus pneumoniae'' hyaluronate lyase Hyl (PDB ID: 4D0Q). The structure is rotated 90 degrees to illustrate the overall fold and the arrangement of β-sheet.]]
-* '''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:''
+CBM70 domains are commonly found as accessory modules in hyaluronate lyases produced by bacteria of the ''Streptococcus'' genus. These domains enhance the enzyme capability to degrade hyaluronic acid, a crucial component of the host's extracellular matrix. During infection, pathogens such as ''S. pneumoniae'' utilize hyaluronate lyase to break down hyaluronic acid, facilitating bacterial invasion and spread. CBM70 domains boost this process by increasing the binding efficiency of the enzyme, playing a key role in pathogen virulence and contributing to the high specificity of the enzyme for hyaluronic acid. Additionally, CBM70 domains have been effectively utilized in lateral flow immunoassays for the specific detection of hyaluronic acid, demonstrating their potential in diagnostic applications <cite>Xuanwei2022</cite>.
-* '''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.
+The first CBM70 module to be identified (SpCBM70) was from the ''S. pneumoniae'' hyaluronate lyase Hyl.
 ;First Structural Characterization
-:Insert archetype here, possibly including ''very brief'' synopsis.
+The first crystal structure of a CBM70 module was also that of SpCBM70, PDB ID 4D0Q.
 == References ==
 <biblio>
-#Cantarel2009 pmid=18838391
+#Michael2014 pmid=25100731
-#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. [https://doi.org/10.1042/BIO03004026 DOI:10.1042/BIO03004026].
-#Boraston2004 pmid=15214846
+#Xuanwei2022 pmid=36395930
-#Hashimoto2006 pmid=17131061
-#Shoseyov2006 pmid=16760304
-#Guillen2010 pmid=19908036
-#Armenta2017 pmid=28547780
 </biblio>