Affiliation:
1. Center of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, China
2. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
Abstract
Metuximab is the generic name of Licartin, a new drug for radioimmunotherapy of hepatocellular carcinoma. Although it is known to be a mouse monoclonal antibody against CD147, the complete epitope mediating the binding of metuximab to CD147 remains unknown. We panned the Ph.D.-12 phage display peptide library against metuximab and got six mimotopes. The following bioinformatics analysis based on mimotopes suggested that metuximab recognizes a conformational epitope composed of more than 20 residues. The residues of its epitope may include T28, V30, K36, L38, K57, F74, D77, S78, D79, D80, Q81, G83, S86, N98, Q100, L101, H102, G103, P104, V131, P132, and K191. The homology modeling of metuximab and the docking of CD147 to metuximab were also performed. Based on the top one docking model, the epitope was predicted to contain 28 residues: AGTVFTTV (23–30), I37, D45, E84, V88, EPMGTANIQLH (92–102), VPP (131–133), Q164, and K191. Almost half of the residues predicted on the basis of mimotope analysis also appear in the docking result, indicating that both results are reliable. As the predicted epitopes of metuximab largely overlap with interfaces of CD147-CD147 interactions, a structural mechanism of metuximab is proposed as blocking the formation of CD147 dimer.
Funder
National Natural Science Foundation of China
Subject
Applied Mathematics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,Modelling and Simulation,General Medicine
Cited by
12 articles.
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