1y2n

Theoretical Model: The protein structure described on this page was determined theoretically, and hence should be interpreted with caution.

MODEL STRUCTURE OF TRASTUZUMAB COMPLEXED WITH H98, A MIMIC ANTIGEN EPITOPE OF HER-2

spinqualitylabelsall models 1y2n Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, PDBsum, ProSAT Publication Abstract from PubMed Trastuzumab, a humanized antibody to HER-2, has been shown to be effective in the treatment of breast cancer in which HER-2 overexpression and metastasis occurs. In our search for an effective mimic epitope of HER-2 binding with trastuzumab and to develop HER-2 peptide vaccine, we screened a phage display 12-mer peptide library with trastuzumab as the target. A mimetic peptide (mimotope) H98 (LLGPYELWELSH) that could specifically recognize trastuzumab was isolated. The DNA encoding peptide H98 was cloned and expressed as the fusion protein GST-H98 in Escherichia coli BL21. The purified GST-H98 could specifically bind to trastuzumab and block the binding of trastuzumab to HER-2 protein. Moreover, H98 could significantly block the function of trastuzumab inhibiting the growth of cancer cells. Mice that were immunized with GST-H98 made specific antibody to H98 as well as to HER-2. In addition, T-cell proliferation occurred in mice immunized with GST-H98. Although no sequence homology was found between H98 and HER-2, through the use of structure analysis we were able to determine that peptide H98 contributed to a conformational epitope of HER-2. Furthermore, we determined that the last two amino acids at the C terminus, and the third together with the fourth amino acid at the N terminus of peptide H98 are critical to the binding of H98 to trastuzumab. As a result, we conclude that peptide H98 has potential for being developed as a HER-2 vaccine for biotherapy of cancer with HER-2 overexpression. A novel peptide isolated from a phage display peptide library with trastuzumab can mimic antigen epitope of HER-2.,Jiang B, Liu W, Qu H, Meng L, Song S, Ouyang T, Shou C J Biol Chem. 2005 Feb 11;280(6):4656-62. Epub 2004 Nov 9. PMID:15536075 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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