6p79 | pdb_00006p79

Engineered single chain antibody C9+C14 ScFv

spinqualitylabelsall models 6p79, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6p79 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We used the molecular modeling program Rosetta to identify clusters of amino acid substitutions in antibody fragments (scFvs and scAbs) that improve global protein stability and resistance to thermal deactivation. Using this methodology, we increased the melting temperature (Tm) and resistance to heat treatment of an antibody fragment that binds to the Clostridium botulinum hemagglutinin protein (anti-HA33). Two designed antibody fragment variants with two amino acid replacement clusters, designed to stabilize local regions, were shown to have both higher Tm compared to the parental scFv and importantly, to retain full antigen binding activity after 2 hours of incubation at 70 degrees C. The crystal structure of one thermostabilized scFv variants was solved at 1.6 A and shown to be in close agreement with the RosettaAntibody model prediction. Computer-based Engineering of Thermostabilized Antibody Fragments.,Lee J, Der BS, Karamitros CS, Li W, Marshall NM, Lungu OI, Miklos AE, Xu J, Kang TH, Lee CH, Tan B, Hughes RA, Jung ST, Ippolito GC, Gray JJ, Zhang Y, Kuhlman B, Georgiou G, Ellington AD AIChE J. 2020 Mar;66(3). doi: 10.1002/aic.16864. Epub 2019 Nov 19. PMID:32336757 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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