Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking

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 pepti...

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Main Authors: Bifang He, Canquan Mao, Beibei Ru, Hesong Han, Peng Zhou, Jian Huang
Format: Article
Language:English
Published: Hindawi Limited 2013-01-01
Series:Computational and Mathematical Methods in Medicine
Online Access:http://dx.doi.org/10.1155/2013/983829
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spelling doaj-a0bb1cf729aa4994a078d69b2734994d2020-11-24T20:55:22ZengHindawi LimitedComputational and Mathematical Methods in Medicine1748-670X1748-67182013-01-01201310.1155/2013/983829983829Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular DockingBifang He0Canquan Mao1Beibei Ru2Hesong Han3Peng Zhou4Jian Huang5Center of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, ChinaSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ChinaCenter of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, ChinaSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ChinaCenter of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, ChinaCenter of Bioinformatics (COBI), Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu 610054, ChinaMetuximab 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.http://dx.doi.org/10.1155/2013/983829
collection DOAJ
language English
format Article
sources DOAJ
author Bifang He
Canquan Mao
Beibei Ru
Hesong Han
Peng Zhou
Jian Huang
spellingShingle Bifang He
Canquan Mao
Beibei Ru
Hesong Han
Peng Zhou
Jian Huang
Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking
Computational and Mathematical Methods in Medicine
author_facet Bifang He
Canquan Mao
Beibei Ru
Hesong Han
Peng Zhou
Jian Huang
author_sort Bifang He
title Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking
title_short Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking
title_full Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking
title_fullStr Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking
title_full_unstemmed Epitope Mapping of Metuximab on CD147 Using Phage Display and Molecular Docking
title_sort epitope mapping of metuximab on cd147 using phage display and molecular docking
publisher Hindawi Limited
series Computational and Mathematical Methods in Medicine
issn 1748-670X
1748-6718
publishDate 2013-01-01
description 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.
url http://dx.doi.org/10.1155/2013/983829
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