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2gjj

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{{STRUCTURE_2gjj| PDB=2gjj | SCENE= }}
{{STRUCTURE_2gjj| PDB=2gjj | SCENE= }}
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'''Crystal structure of a single chain antibody scA21 against Her2/ErbB2'''
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===Crystal structure of a single chain antibody scA21 against Her2/ErbB2===
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==Overview==
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Anti-ErbB2 antibodies targeting distinct epitopes can have different biological functions on cancer cells. A21 prepared by surface epitope masking (SEM) method is a tumor-inhibitory anti-ErbB2 monoclonal antibody. Previously we engineered a single chain chimeric antibody chA21 with potential for therapy of ErbB2-overexpressing tumors. Here, we mapped the A21 epitope on ErbB2 extracellular domain (ECD) by screening a combinatorial phage display peptide library, serial subdomain deletion, and mutagenesis scanning. X-ray crystal structure of the A21 scFv fragment at 2.1 A resolution was also determined. A molecular model of Ag-Ab complex was then constructed based on the crystal structures of the A21 scFv and ErbB2 ECD. Some of biological functions of the A21 mAb and its derivative antibodies including their tumor cell growth inhibition and effects on the expression, internalization, and phosphorylation of ErbB2 receptor were also investigated. The results showed that A21 recognized a conformational epitope comprising a large region mostly from ErbB2 extracellular subdomain I with several surface-exposed residues important for the binding affinity. These data provide unique functional properties of A21 that are quite different from two broadly used anti-ErbB2 mAbs, Herceptin and 2C4. It suggested that the A21 epitope may be another valuable target for designing new anti-ErbB2 therapeutics.
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(as it appears on PubMed at http://www.pubmed.gov), where 17847085 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17847085}}
==About this Structure==
==About this Structure==
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[[Category: Immune system]]
[[Category: Immune system]]
[[Category: Scfv]]
[[Category: Scfv]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:10:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:52:33 2008''

Revision as of 03:52, 29 July 2008

Image:2gjj.png

Template:STRUCTURE 2gjj

Crystal structure of a single chain antibody scA21 against Her2/ErbB2

Template:ABSTRACT PUBMED 17847085

About this Structure

2GJJ is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Epitope mapping and structural analysis of an anti-ErbB2 antibody A21: Molecular basis for tumor inhibitory mechanism., Hu S, Zhu Z, Li L, Chang L, Li W, Cheng L, Teng M, Liu J, Proteins. 2008 Feb 15;70(3):938-49. PMID:17847085

Page seeded by OCA on Tue Jul 29 06:52:33 2008

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