Bacterial enzymes, serving as potent catalysts with versatile applications in diverse mammalian metabolic functions, represent a significant area of interest in molecular science. Chondroitinase ABC (chABC) derived from Proteus vulgaris is one such enzyme that has gained attention for its capacity to cleave chondroitin sulfate (CS) glycosaminoglycans (GAGs) from various proteoglycans such as Aggrecan, Neurocan, Decorin. The substrate specificity of chABC is well-known for targeting various structural motifs of CS chains and has gained immense popularity in the By breaking down inhibitory CS GAG chains in the extracellular matrix, chondroitinase has been known to facilitate neuroplasticity thus offering a promising avenue for the treatment of traumatic brain injuries(1).
Within this context, our investigation into the biochemistry of chABC led us to a previously unreported inhibition of chABC activity by the polysaccharide Dextran Sulfate Sodium (DSS). To investigate the possible action of other polysaccharides on chABC digestion of CS chains, we compared the inhibitory effects of various other polysaccharides such as heparan sulfate, heparin, colominic acid, fucoidan and dextran. This analysis helped identify key structural features that influence chondroitinase inhibition since remarkably, DSS emerged as the unique polysaccharide inhibitor of chABC. Distinct chABC inhibitory effects correlated with DSS chain length as determined using a plate-based colorimetric assay using WST-1 dye that involves a reductive reaction leading to a formation of coloured formazan(2). DSS has been extensively used to induce ulcerative colitis in mice to effectively mimic inflammatory bowel disease (IBD) in humans, as well as having previously been shown to inhibit both polymerase and reverse transcriptase activities (3). Our results therefore show the added effects of DSS and emphasize the specific ability of DSS to inhibit bacterial chABC activity. This work provides insights into the strategic design and utilization of DSS for the purpose of modulating bacterial chondroitinase activity on the human extracellular matrix.