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The CBM70 family comprises members predominantly of bacterial origin [1]. Notably, it is the only known family with a specific binding affinity for hyaluronic acid, a linear glycosaminoglycan composed of the repeating disaccharide unit 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 [2].
Structural Features
CBM70 modules are typically composed of approximately 160 amino acids. The crystal structure of the N-terminal CBM70 module (SpCBM70) from the Streptococcus 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. This groove, which is similar to the binding site observed in β-sandwich CBMs such as those in the CBM4 family, is the putative hyaluronan-binding site [3]. Structural studies and mutational analysis have identified key residues, including a conserved solvent-exposed tryptophan and several basic residues, that are essential for hyaluronan recognition, supporting its classification as a Type B CBM [1].
Figure 1. The fold of the hyaluronic acid binding molecule SpCBM70 from the Streptococcus pneumoniae hyaluronate lyase Hyl 4D0Q. The structure is rotated 90 degrees to illustrate the overall fold and the arrangement of the β-sheets [1].
Functionalities
CBM70 domains are commonly found as accessory modules in hyaluronate lyases produced by bacteria of the Streptococcus genus, such as Hyl from the PL8 family [4, 5]. These domains enhance the enzyme capability to degrade hyaluronic acid, a crucial component of the host's extracellular matrix [6]. Infection by pathogens such as S. pneumoniae utilize hyaluronate lyase to break down hyaluronic acid, facilitating bacterial invasion and spread [7]. 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 [8]. Additionally, the CBM70 family member SrCBM70 has been effectively utilized in lateral flow immunoassays for the specific detection of hyaluronic acid, demonstrating its 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 [1].
First Structural Characterization
The first crystal structure of a CBM70 module was also that of SpCBM70, PDB ID 4D0Q [1].
