9q0p

Human anti-EBV gH/gL Fab (AMMO1) with G111T light chain mutation

spinqualitylabelsall models 9q0p, resolution 2.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9q0p 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 2.08Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Monoclonal antibodies with lambda (lambda) light chains are less commonly used in therapeutics due to their lower biophysical stability compared to kappa (kappa) variants. Here, we identify a conserved glycine residue (Gly111) in the lambda light chain hinge as a driver of large-scale Fab elbow-angle transitions. Using microsecond-scale molecular dynamics simulations of the EBV-neutralizing Fab AMMO1, we show that substituting Gly111 with threonine (G111T) increases the free energy barrier between conformational states, effectively arresting these transitions. Structural and biophysical analyses-including crystallography, differential scanning fluorimetry, and surface plasmon resonance-confirm that the mutation maintains Fab architecture and antigen binding while increasing thermal stability by up to 2.5 degrees C. The same mutation applied to a second lambda-Fab yielded similar stabilization, and simulations of three clinical lambda-Fabs revealed consistent reductions in elbow-angle flexibility. These results demonstrate a generalizable, single-residue engineering strategy to enhance the stability of lambda-based Fabs without compromising function, with direct implications for therapeutic antibody development and manufacturability. Single-residue engineering of lambda (lambda) antibody light chains reduces conformational flexibility and enhances thermal stability.,Jewel Y, Young T, Park M, Ly K, Gonzalez A, Mallett TC, Williams JC Comput Struct Biotechnol J. 2025 Oct 24;27:4730-4739. doi: , 10.1016/j.csbj.2025.10.045. eCollection 2025. PMID:41245890 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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