2XA8

Crystal structure of the Fab domain of omalizumab at 2.41A

Summary for 2XA8

• Entry DOI: 10.2210/pdb2xa8/pdb
• Descriptor: OMALIZUMAB HEAVY CHAIN, OMALIZUMAB LIGHT CHAIN (3 entities in total)
• Functional Keywords: xolair, allergy, immune system
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 47220.26

Authors

Huang, C.H.,Hung, F.H.A.,Lim, C.,Chang, T.W.,Ma, C. (deposition date: 2010-03-30, release date: 2011-05-11, Last modification date: 2024-10-16)

Primary citation

Wright, J.D.,Chu, H.M.,Huang, C.H.,Ma, C.,Chang, T.W.,Lim, C.
Structural and Physical Basis for Anti-IgE Therapy.
Sci Rep, 5:11581-11581, 2015

PubMed Abstract: Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcεRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcεRI and omalizumab-binding sites in the Cε3 domain, but crystallographic studies show FcεRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-Å omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcεRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcεRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcεRI.

PubMed: 26113483
DOI: 10.1038/srep11581

Experimental method

X-RAY DIFFRACTION (2.42 Å)