Sökning: onr:"swepub:oai:DiVA.org:sh-15748" >
Functional probing ...
Functional probing of the human glucocorticoid receptor steroid-interacting surface by site-directed mutagenesis - Gln-642 plays an important role in steroid recognition and binding
- Artikel/kapitelEngelska2000
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:sh-15748
-
https://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-15748URI
-
https://doi.org/10.1074/jbc.M000228200DOI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:1956357URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
To elucidate which amino acids in the glucocorticoid receptor ligand-binding domain might be involved in determining steroid binding specificity by interaction with the D-ring of glucocorticoids, we have performed site-directed mutagenesis of the four amino acids Met-560, Met-639, Gln-642, and Thr-739 based on their proximity to the steroid in a model structure. Mutations of these residues affected steroid binding affinity, specificity, and/or steroid-dependent transactivation. The results indicate that these residues are located in close proximity to the ligand and appear to play a role in steroid recognition and/or transactivating sensitivity, possibly by changes in the steroid-dependent conformational change of this region, resulting in the formation of the AF-2 site. Mutation of Gln-642 resulted in a marked decrease in affinity for steroids containing a 17 alpha-OH group. This effect was alleviated by the presence of a 16 alpha-CH3 group to a varying degree. Thr-739 appears to form a hydrogen bond with the 21-OH group of the steroid, as well as possibly forming hydrophobic interactions with the steroid, Met-EGO and Met-639 appear to form hydrophobic interactions with the D-ring of the steroid, although the nature of these interactions cannot be characterized in more detail at this point.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Greenidge, P
(författare)
-
Gillner, M
(författare)
-
Koehler, K F
(författare)
-
Wright, Anthony P HKarolinska Institutet,Södertörns högskola,Avdelning Naturvetenskap,Karolinska Institute(Swepub:sh)SHAYWT
(författare)
-
Carlstedt-Duke, JKarolinska Institutet
(författare)
-
Södertörns högskolaAvdelning Naturvetenskap
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Journal of Biological Chemistry275:25, s. 19041-190490021-92581083-351X
Internetlänk
Hitta via bibliotek
Till lärosätets databas