9pz6
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Anti-NANP Fab with G112T light chain mutation== | |
| + | <StructureSection load='9pz6' size='340' side='right'caption='[[9pz6]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9pz6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PZ6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9pz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pz6 OCA], [https://pdbe.org/9pz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pz6 RCSB], [https://www.ebi.ac.uk/pdbsum/9pz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pz6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:41245890</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Young | + | <div class="pdbe-citations 9pz6" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Young T]] | ||
Current revision
Anti-NANP Fab with G112T light chain mutation
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