Linked Life Data

8234236

Source:http://linkedlifedata.com/resource/pubmed/id/8234236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-12-8
pubmed:abstractText
The highly conserved asparagine residue at position 32 (Asn32) in the 'hinge' region of epidermal growth factor (EGF) separates the N- and C-terminal structural motifs of the EGF molecule and is therefore an appropriate target for structure-function studies. Analogs of human EGF (hEGF) were generated in which Asn32 was substituted with aspartate, glycine, isoleucine, lysine, proline and tryptophan. The relative affinity of the EGF receptor for mutant hEGF analogs was determined by radioreceptor competition assay. A wide range of receptor affinities was observed depending on the amino acid substitution. N32K and N32W hEGF analogs had relatively high receptor affinity, while the N32G and N32D analogs showed decreased affinity, 35% and 25% respectively, relative to wild type hEGF. However, no binding of the N32P analog was detected by radioreceptor competition assay. The N32P mutant displayed an NMR spectrum significantly different from that of native wild type hEGF, indicating gross structural perturbation. In contrast, the N32K and N32D analogs exhibited spectra similar to that of native wild type hEGF. Genetically combining the N32D hEGF with an hEGF species having either the mutation L26G in the N-terminal region or L47A in the C-terminal region, generated double-mutant hEGF species which had relative affinities essentially equal to the product of the relative affinities of the parent hEGF mutants, indicating functionally independent changes in ligand-receptor interaction. These studies indicate the requirement for H-bond donor functionality in the side chain of residue number 32 in forming a fully competent receptor-binding epitope.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0269-2139
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
651-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
The role of asparagine-32 in forming the receptor-binding epitope of human epidermal growth factor.
pubmed:affiliation
Protein Engineering and Molecular Mutagenesis Program, Oak Ridge Graduate School of Biomedical Sciences, TN.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't