1n8z

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[[Image:1n8z.jpg|left|200px]]
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{{Seed}}
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[[Image:1n8z.png|left|200px]]
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{{STRUCTURE_1n8z| PDB=1n8z | SCENE= }}
{{STRUCTURE_1n8z| PDB=1n8z | SCENE= }}
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'''Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab'''
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===Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab===
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==Overview==
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HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies.
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The line below this paragraph, {{ABSTRACT_PUBMED_12610629}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12610629 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12610629}}
==About this Structure==
==About this Structure==
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[[Category: Cell surface receptor]]
[[Category: Cell surface receptor]]
[[Category: Tyrosin kinase receptor]]
[[Category: Tyrosin kinase receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:14:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:14:01 2008''

Revision as of 03:14, 29 July 2008

Template:STRUCTURE 1n8z

Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab

Template:ABSTRACT PUBMED 12610629

About this Structure

1N8Z is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab., Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ, Nature. 2003 Feb 13;421(6924):756-60. PMID:12610629

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