Molecular insights into the interaction between human nicotinamide phosphoribosyltransferase and Toll-like receptor 4.

ABSTRACT: The secreted form of the enzyme nicotinamide phosphoribosyltransferase (NAMPT), which catalyzes a key reaction in intracellular NAD biosynthesis, acts as a damage-associated molecular pattern triggering Toll-like receptor 4 (TLR4)-mediated inflammatory responses. However, the precise mechanism of interaction is unclear. Using an integrated approach combining bioinformatics and functional and structural analyses, we investigated the interaction between NAMPT and TLR4 at the molecular level. Starting from previous evidence that the bacterial ortholog of NAMPT cannot elicit the inflammatory response, despite a high degree of structural conservation, two positively charged areas unique to the human enzyme (the α1-α2 and β1-β2 loops) were identified as likely candidates for TLR4 binding. Howeve

SUBMITTER: Gasparrini M 

PROVIDER: S-EPMC8892085 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature