Identification of conformational core epitope Lys68 in CSa based on the 3-D modeling complex C5a and its functional antibody F20
Inhibition of C5a by antibodies has been demonstrated to dramatically improve survival in various sepsis models in mice and rats.The structural basis of C5a mediated bioactivity and C5a antibody mediated neutralization are of interesting to be investigated.In the previous study,we obtained a novel functional mouse antibody named a5 F20.With computer-guided modeling method,the 3-D theoretical structure of F20 Fv fragment was constructed.Using the crystal structure of C5a,the 3-D complex structure of C5a and F20 Fv fragment was modeled with molecular docking method.Based on distance geometry method and intermolecular interaction theory,the key residue Lys68 in C5a identified by F20 was predicted.The mutant experimental results showed that the residue Lys68 was the critical residue of C5a for its bioactivity and F20 binding activity.The present study shed new light on the structural basis of C5a mediated bioactivity.The identification of the critical residue will provide useful information for human complement C5a targeted therapeutic intervention.
C5a Computer modeling Molecular docking
Huawei Wei Beifen Shen Yan Li Zhou Lin Jiannan Feng Hui Peng Renfeng Guo Gencheng Han Shusheng Geng Xiaoling Lang Yingxun Sun
Department of Immunology,Institute of Basic Medical Sciences,Beijing,China Department of Immunology,Institute of Basic Medical Sciences,Beijing,China ;Department of Immunology Department of Pathology, University of Michigan Medical School.Ann Arbor, MI, USA Beijing Mabworks Biotech Co., Ltd, Beijing China
国际会议
南京
英文
298-304
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）