Linked Life Data

16531225

Source:http://linkedlifedata.com/resource/pubmed/id/16531225

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-3-13
pubmed:databankReference
pubmed:abstractText
In this work, we combined computational protein-protein docking with computational and experimental mutagenesis to predict the structure of the complex formed by monoclonal antibody 806 (mAb 806) and the epidermal growth factor receptor (EGFR). We docked mAb 806, an antitumor antibody, to its epitope of EGFR residues 287-302. Potential mAb 806-EGFR orientations were generated, and computational mutagenesis was used to filter them according to their agreement with experimental mutagenesis data. Further computational mutagenesis suggested additional mutations, which were tested to arrive at a final structure that was most consistent with experimental mutagenesis data. We propose that this is the EGFR-mAb 806 structure, in which mAb 806 binds to an untethered form of the receptor, consistent with published experimental results. The steric hindrance created by the antibody near the EGFR dimer interface interferes with receptor dimerization, and we postulate this as the structural origin for the antitumor effect of mAb 806.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0969-2126
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
401-14
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Structural model of the mAb 806-EGFR complex using computational docking followed by computational and experimental mutagenesis.
pubmed:affiliation
Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural