Perturbing dimer interactions and allosteric communication modulates the immunosuppressive activity of human galectin-7.

ABSTRACT: The design of allosteric modulators to control protein function is a key objective in drug discovery programs. Altering functionally essential allosteric residue networks provides unique protein family subtype specificity, minimizes unwanted off-target effects, and helps avert resistance acquisition typically plaguing drugs that target orthosteric sites. In this work, we used protein engineering and dimer interface mutations to positively and negatively modulate the immunosuppressive activity of the proapoptotic human galectin-7 (GAL-7). Using the PoPMuSiC and BeAtMuSiC algorithms, mutational sites and residue identity were computationally probed and predicted to either alter or stabilize the GAL-7 dimer interface. By designing a covalent disulfide bridge between protomers to control homod

SUBMITTER: Pham NTH 

PROVIDER: S-EPMC8592873 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature