Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
23
|
pubmed:dateCreated |
1994-7-13
|
pubmed:abstractText |
Characterization of murine-human hybrid interferon-gamma (IFN-gamma) molecules suggests that substitution of the peptide connecting the A and B helices in human IFN-gamma with the murine sequence significantly blocks the protein's binding to the human interferon-gamma receptor. Mutagenesis showed that this effect is localized to the central part of this A-B loop peptide, particularly Ser20, Asp21, Val22, and Ala23. One mutant, IFN-gamma/A23E,D24E,N25K, was examined by NMR. This "EEK" mutation does not significantly alter the conformation of interferon-gamma, suggesting that the effects of these mutations are not the result of global conformational changes. The A-B loop is near histidine 111, a residue previously shown to be important in receptor-ligand interaction (Lunn, C. A., Fossetta, J., Dalgarno, D., Murgolo, N., Windsor, W., Zavodny, P. J., Narula, S. K., and Lundell, D. (1992) Protein Eng. 5, 253-257). We show that copper forms a complex between histidine 19 in the A-B loop and histidine 111. This metal complex lacks the ability to interact with the interferon-gamma receptor. These results suggest that the A-B loop contains important structural information needed for receptor-ligand binding and hence biological activity of human interferon-gamma.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Metals,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
0021-9258
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
10
|
pubmed:volume |
269
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
16159-62
|
pubmed:dateRevised |
2008-11-21
|
pubmed:meshHeading |
pubmed-meshheading:8206916-Amino Acid Sequence,
pubmed-meshheading:8206916-Animals,
pubmed-meshheading:8206916-DNA Mutational Analysis,
pubmed-meshheading:8206916-Dose-Response Relationship, Drug,
pubmed-meshheading:8206916-Humans,
pubmed-meshheading:8206916-Interferon-gamma,
pubmed-meshheading:8206916-Metals,
pubmed-meshheading:8206916-Mice,
pubmed-meshheading:8206916-Molecular Sequence Data,
pubmed-meshheading:8206916-Protein Binding,
pubmed-meshheading:8206916-Receptors, Interferon,
pubmed-meshheading:8206916-Recombinant Fusion Proteins,
pubmed-meshheading:8206916-Species Specificity,
pubmed-meshheading:8206916-Structure-Activity Relationship
|
pubmed:year |
1994
|
pubmed:articleTitle |
Importance of the loop connecting A and B helices of human interferon-gamma in recognition by interferon-gamma receptor.
|
pubmed:affiliation |
Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
|
pubmed:publicationType |
Journal Article,
Comparative Study
|