“…This is, for example, the case for the human estrogenic type 1 17β-HSD (h17β-HSD1), a member of the SDR superfamily that maintains the steroid in an almost closed cavity and stabilizes it by hydrogen bonds with polar atoms at both ends (O3 and O17) (Figure 1(c)) in addition to several hydrophobic interactions involving hydrophobic residues located all around the steroid nucleus. 10 The steroid hormone receptors also bind their steroid ligands this way [24][25][26] and the importance of these interactions established by the receptors with the extremities of the steroid molecules (Figure 1(d)) could greatly account for the high binding affinity for their steroidal ligands. 27 Moreover, the elimination of one of these interactions has been found to alter the specificity of the receptor toward its ligands in addition to changing its functional activity.…”
“…This is, for example, the case for the human estrogenic type 1 17β-HSD (h17β-HSD1), a member of the SDR superfamily that maintains the steroid in an almost closed cavity and stabilizes it by hydrogen bonds with polar atoms at both ends (O3 and O17) (Figure 1(c)) in addition to several hydrophobic interactions involving hydrophobic residues located all around the steroid nucleus. 10 The steroid hormone receptors also bind their steroid ligands this way [24][25][26] and the importance of these interactions established by the receptors with the extremities of the steroid molecules (Figure 1(d)) could greatly account for the high binding affinity for their steroidal ligands. 27 Moreover, the elimination of one of these interactions has been found to alter the specificity of the receptor toward its ligands in addition to changing its functional activity.…”
“…Among nuclear receptors, the AR AF-2 domain shows a distinct preference for FxxLF motifs, found in co-activators of the AR-associated protein (ARA) family and in the AR N-terminus (amino acids [23][24][25][26][27]) [36]. Examination of the crystal structures of the AR ligand-binding domain [33][34][35] can help to rationalise the effect of mutations on the transactivation profile of the receptor.…”
Section: Discussionmentioning
confidence: 99%
“…Crystallographic studies have recently revealed essential insights into the three-dimensional structure of the AR ligand-binding domain [33][34][35]. All ligand-binding domains of nuclear receptors share a common structure, which can be described as a three-layer ␣-helical sandwich composed of up to 12 ␣-helices [36].…”
“…The hydrophobic difference field shows the differences between progesterone and androgen receptor near residue Thr894(PR)/ Leu880(AR). This difference is caused by higher polarity of Thr877 in AR compared to Cys891 in PR and the larger space occupied by the hydrophobic side-chain of Leu880 in AR, and has been used to explain the specificity for certain ligands [41].…”
Section: Pairwise Comparison Of Androgen and Progesterone Receptorsmentioning
confidence: 99%
“…Both receptors show a positive polar contour at 2.1 Å distance from the backbone carbonyl group of Leu887(PR)/Leu873(AR) and 3.8 Å distance from the backbone nitrogen of Cys891, which is not targeted by the present ligands. Important ligand-receptor interactions and differences in these regions are identified by our method [41,42]. The difference between the two NR binding sites originates mainly from the Cys891/Thr877 and Thr894/Leu880 mutations.…”
Section: Pairwise Comparison Of Androgen and Progesterone Receptorsmentioning
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