4LLY

Crystal structure of Pertuzumab Clambda Fab with variable and constant domain redesigns (VRD2 and CRD2) at 1.6A

Summary for 4LLY

• Entry DOI: 10.2210/pdb4lly/pdb
• Related: 4LLD 4LLM 4LLQ 4LLU 4LLW
• Descriptor: mutated Pertuzumab Fab heavy chain, light chain Clambda, GLYCEROL, ... (5 entities in total)
• Functional Keywords: fab, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 94671.85

Authors

Pustilnik, A.,Lewis, S.M.,Wu, X.,Sereno, A.,Huang, F.,Guntas, G.,Leaver-Fay, A.,Smith, E.M.,Ho, C.,Hansen-Estruch, C.,Chamberlain, A.K.,Truhlar, S.M.,Kuhlman, B.,Demarest, S.J.,Atwell, S. (deposition date: 2013-07-09, release date: 2014-01-29, Last modification date: 2024-10-30)

Primary citation

Lewis, S.M.,Wu, X.,Pustilnik, A.,Sereno, A.,Huang, F.,Rick, H.L.,Guntas, G.,Leaver-Fay, A.,Smith, E.M.,Ho, C.,Hansen-Estruch, C.,Chamberlain, A.K.,Truhlar, S.M.,Conner, E.M.,Atwell, S.,Kuhlman, B.,Demarest, S.J.
Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.
Nat.Biotechnol., 32:191-198, 2014

PubMed Abstract: Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.

PubMed: 24463572
DOI: 10.1038/nbt.2797

Experimental method

X-RAY DIFFRACTION (1.6 Å)