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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
38
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pubmed:dateCreated |
1995-10-17
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pubmed:abstractText |
We showed previously that replacement of Lys-145 in the IL-1 receptor antagonist (IL-1ra) with Asp resulted in an analog (IL-1ra K145D) with partial agonist activity. To identify additional amino acids that affect IL-1 bioactivity, we created second site mutations in IL-1ra K145D. Substitutions of single amino acids surrounding position 145 were made; none of these substitutions increased the bioactivity of IL-1ra K145D. However, the insertion of the beta-bulge (QGEESN) of IL-1 beta at the corresponding region of IL-1ra K145D resulted in a 3-4-fold augmentation of bioactivity. An additional increase in agonist activity was observed when the beta-bulge was co-expressed with a second substitution (His-54 --> Pro) in IL-1ra K145D. We also show that the bioactivity of both IL-1ra K145D and the triple mutant IL-1ra K145D/H54P/QGEESN is dependent on interaction with the newly cloned IL-1 receptor accessory protein.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/IL1RN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin 1 Receptor Antagonist...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
22
|
pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22460-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7673234-Amino Acid Sequence,
pubmed-meshheading:7673234-Binding, Competitive,
pubmed-meshheading:7673234-Cell Division,
pubmed-meshheading:7673234-Humans,
pubmed-meshheading:7673234-Interleukin 1 Receptor Antagonist Protein,
pubmed-meshheading:7673234-Interleukin-1,
pubmed-meshheading:7673234-Models, Molecular,
pubmed-meshheading:7673234-Molecular Sequence Data,
pubmed-meshheading:7673234-Protein Binding,
pubmed-meshheading:7673234-Protein Structure, Tertiary,
pubmed-meshheading:7673234-Receptors, Interleukin-1,
pubmed-meshheading:7673234-Sialoglycoproteins,
pubmed-meshheading:7673234-Structure-Activity Relationship
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pubmed:year |
1995
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pubmed:articleTitle |
Insertion of a structural domain of interleukin (IL)-1 beta confers agonist activity to the IL-1 receptor antagonist. Implications for IL-1 bioactivity.
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pubmed:affiliation |
Department of Inflammation/Autoimmune Diseases, Hoffman-La Roche Inc., Nutley, New Jersey 07110, USA.
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pubmed:publicationType |
Journal Article,
In Vitro
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