Background: Interaction between HIV gp120 and cell CD4 initiates viral infection of host cells. Results: Only CD4 with reduced disulfides in domain 1 or 2 binds gp120, which inhibits thioredoxin-dependent CD4 dimerization. Conclusion: Cell surface oxidoreductases may prime CD4 for gp120 engagement, and impairment of redox-driven CD4 dimerization by gp120 may compromise CD4 function. Significance: Redox-dependent isomerization of CD4 is critical for HIV entry.
The Polysaccharide Lyase Family 6 (PL6) represents one of the 41 polysaccharide lyase families classified in the CAZy database with the vast majority of its members being alginate lyases grouped into three subfamilies, PL6_1–3. To decipher the mode of recognition and action of the enzymes belonging to subfamily PL6_1, we solved the crystal structures of Pedsa0632, Patl3640, Pedsa3628 and Pedsa3807, which all show different substrate specificities and mode of action (endo−/exo-lyase). Thorough exploration of the structures of Pedsa0632 and Patl3640 in complex with their substrates as well as docking experiments confirm that the conserved residues in subsites −1 to +3 of the catalytic site form a common platform which can accommodate various types of alginate in a very similar manner but with a series of original adaptations bringing them their specificities of action. From comparative studies with existing structures of PL6_1 alginate lyases, we observe that in the right-handed parallel β-helix fold shared by all these enzymes, the substrate binding site harbors the same overall conserved structures and organization. Despite this apparent similarity, it appears that members of the PL6_1 subfamily specifically accommodate and catalyze the degradation of different alginates suggesting that this common platform is actually a highly adaptable and specific tool.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.