The dual binding of pantoprazole mitigates ceftriaxone-mediated misfolding of human serum albumin.

Proton pump inhibitors (PPIs) like pantoprazole are often prescribed alongside antibiotics to prevent antibiotic-induced gastritis, ulcers, and microbiome disturbances. In this study, we provide the first evidence of pantoprazole's (PTP) distinct protective role in preventing ceftriaxone (CTX) induced structural alterations and aggregation of human serum albumin (HSA). We have found strong binding of pantoprazole at domain-I and domain-III, whereas ceftriaxone binds in domain-II of HSA. The ceftriaxone binding was found to disrupt the tertiary structure of the protein and induces the non-native β-structures without affecting the thermal stability of the protein. Moreover, it was found to promote the thermal-induced formation of protofibrils. However, the addition of pantoprazole in HSA-CTX complex efficiently restored the structural alterations and aggregation reaction. This study highlights a previously unrecognized protective role of PPIs, particularly pantoprazole, in preserving protein structure and aggregation caused by antibiotic overuse.