6vts

Crystal structure of G16S human Galectin-7 mutant in complex with lactose

spinqualitylabelsall models 6vts, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vts is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: GAL, GLC, GOL, PRD_900008 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LEG7_HUMAN Publication Abstract from PubMed 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 homodimer strength and stability, we demonstrate the importance of dimer interface perturbations on the allosteric network bridging the two opposite glycan-binding sites on GAL-7, resulting in control of induced apoptosis in Jurkat T cells. Molecular investigation of G16X GAL-7 variants using X-ray crystallography, biophysical, and computational characterization illuminates residues involved in dimer stability and allosteric communication, along with discrete long-range dynamic behaviors involving loops 1, 3, and 5. We show that perturbing the protein-protein interface between GAL-7 protomers can modulate its biological function, even when the overall structure and ligand-binding affinity remains unaltered. This study highlights new avenues for the design of galectin-specific modulators influencing both glycan-dependent and glycan-independent interactions. Perturbing dimer interactions and allosteric communication modulates the immunosuppressive activity of human galectin-7.,Pham NTH, Letourneau M, Fortier M, Begin G, Al-Abdul-Wahid MS, Pucci F, Folch B, Rooman M, Chatenet D, St-Pierre Y, Lague P, Calmettes C, Doucet N J Biol Chem. 2021 Oct 19;297(5):101308. doi: 10.1016/j.jbc.2021.101308. PMID:34673030 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Galectin 3D structures

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