共查询到20条相似文献,搜索用时 938 毫秒
1.
M Li X Ye RN Woodward C Zhu LA Nichols LJ Holland 《Canadian Metallurgical Quarterly》1998,273(16):9790-9796
2.
3.
4.
5.
6.
7.
8.
9.
Molecular dynamics study of glucocorticoid receptor-DNA binding 总被引:2,自引:0,他引:2
10.
Gene regulation by steroids is tightly coupled to hormone concentration and stereochemistry. A key step is binding of hormones to receptors which interact with consensus DNA sequences known as hormone response elements (HREs). The specificity and strength of hormone binding do not correlate well with hormonal activity suggesting an additional step involving recognition of ligand by the gene. Stereospecific fit of hormones between base pairs and correlation of fit with hormonal activity led to the proposal that such recognition involves insertion of hormone into DNA. Here, the feasibility of insertion was investigated using computer models of the glucocorticoid receptor DNA binding domain bound to its HRE. The site reported to accommodate glucocorticoids was found in the HRE and was exposed to permit unwinding at this locus. The resulting cavity in the unwound DNA/receptor interface fit cortisol remarkably well; cortisol formed hydrogen bonds to both the receptor and DNA. Current experimental evidence is generally consistent with ligand binding domains of receptors undergoing a conformational change which facilitates transfer of the ligand into the unwound DNA/receptor interface. We propose this step is rate limiting and alterations in receptor, DNA or hormone which attenuate insertion impair hormonal regulation of gene function. 相似文献
11.
PJ Barnes 《Canadian Metallurgical Quarterly》1998,94(6):557-572
12.
13.
14.
15.
16.
17.
18.
19.