6P79

Engineered single chain antibody C9+C14 ScFv

Summary for 6P79

• Entry DOI: 10.2210/pdb6p79/pdb
• Descriptor: Engineered antibody heavy chain, Engineered antibody light chain (3 entities in total)
• Functional Keywords: antibody engineering, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 26798.67

Authors

Zhang, Y.,Li, W.,Marshall, N. (deposition date: 2019-06-05, release date: 2020-04-15, Last modification date: 2024-10-30)

Primary citation

Lee, J.,Der, B.S.,Karamitros, C.S.,Li, W.,Marshall, N.M.,Lungu, O.I.,Miklos, A.E.,Xu, J.,Kang, T.H.,Lee, C.H.,Tan, B.,Hughes, R.A.,Jung, S.T.,Ippolito, G.C.,Gray, J.J.,Zhang, Y.,Kuhlman, B.,Georgiou, G.,Ellington, A.D.
Computer-based Engineering of Thermostabilized Antibody Fragments.
Aiche J, 66:-, 2020

PubMed Abstract: 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 (T) and resistance to heat treatment of an antibody fragment that binds to the 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 T compared to the parental scFv and importantly, to retain full antigen binding activity after 2 hours of incubation at 70 °C. The crystal structure of one thermostabilized scFv variants was solved at 1.6 Å and shown to be in close agreement with the RosettaAntibody model prediction.

PubMed: 32336757
DOI: 10.1002/aic.16864

Experimental method

X-RAY DIFFRACTION (1.583 Å)