Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

8DF1

Chi3l1 bound by antibody C59

Summary for 8DF1
Entry DOI10.2210/pdb8df1/pdb
DescriptorChitinase-3-like protein 1, C59 Fab Heavy chain, C59 Fab Light chain, ... (6 entities in total)
Functional Keywordschi3l1, fab, immunotherapeutic, immune system
Biological sourceHomo sapiens (human)
More
Total number of polymer chains18
Total formula weight524620.76
Authors
Wrapp, D.,McLellan, J.S. (deposition date: 2022-06-21, release date: 2023-03-01, Last modification date: 2024-10-09)
Primary citationLi, L.,Wen, Y.,Wrapp, D.,Jeong, J.,Zhao, P.,Xiong, W.,Atkins, C.L.,Shan, Z.,Hui, D.,McLellan, J.S.,Zhang, N.,Ju, C.,An, Z.
A novel humanized Chi3l1 blocking antibody attenuates acetaminophen-induced liver injury in mice.
Antib Ther, 6:1-12, 2023
Cited by
PubMed Abstract: Acetaminophen (APAP) overdose is a leading cause of acute liver injury in the USA. The chitinase 3-like-1 (Chi3l1) protein contributes to APAP-induced liver injury (AILI) by promoting hepatic platelet recruitment. Here, we report the development of a Chi3l1-targeting antibody as a potential therapy for AILI. By immunizing a rabbit successively with the human and mouse Chi3l1 proteins, we isolated cross-reactive monoclonal antibodies (mAbs) from single memory B cells. One of the human and mouse Chi3l1 cross-reactive mAbs was humanized and characterized in both and biophysical and biological assays. X-ray crystallographic analysis of the lead antibody C59 in complex with the human Chi3l1 protein revealed that the kappa light contributes to majority of the antibody-antigen interaction; and that C59 binds to the 4α-5β loop and 4α-helix of Chi3l1, which is a functional epitope and hotspot for the development of Chi3l1 blocking antibodies. We humanized the C59 antibody by complementarity-determining region grafting and kappa chain framework region reverse mutations. The humanized C59 antibody exhibited similar efficacy as the parental rabbit antibody C59 in attenuating AILI . Our findings validate Chi3l1 as a potential drug target for AILI and provide proof of concept of developing Chi3l1 blocking antibody as a therapy for the treatment of AILI.
PubMed: 36683763
DOI: 10.1093/abt/tbac027
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.3 Å)
Structure validation

226707

PDB entries from 2024-10-30

PDB statisticsPDBj update infoContact PDBjnumon