2r40

[[Image:2r40.gif|left|200px]]<br /><applet load="2r40" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2r40, resolution 2.402&Aring;" />

'''Crystal structure of 20E bound EcR/USP'''<br />

==Overview==

The insect steroid hormone 20-hydroxyecdysone (20E) binds to its cognate, nuclear receptor composed of the ecdysone receptor (EcR) and Ultraspiracle, (USP) and triggers the main developmental transitions, in particular, molting and metamorphosis. We present the crystal structure of the, ligand-binding domains of EcR/USP in complex with 20E at 2.4A resolution, and compare it with published structures of EcR/USP bound to ponasterone A, (ponA). ponA is essentially identical to 20E but lacks the 25-OH group of, 20E. The structure of 20E-bound EcR indicates that an additional hydrogen, bond is formed compared with the ponA-bound receptor, yet, paradoxically, ponA has a significantly higher affinity for EcR than 20E. Theoretical, studies based on docking and free energy methods lead to a rationale for, understanding the difference in binding affinities between 20E and ponA., Results of the calculations indicate that the favorable contribution from, the extra H-bond made by 25-OH of 20E is counterbalanced by its larger, desolvation cost compared with that of ponA. The contribution of 25-OH to, the binding affinity is further compared with those of 20- and 22-OH, groups. Ligands that lack the 20- or 22-OH group are indeed known to bind, less favorably to EcR than 20E, an effect opposite to that observed for, ponA. The results indicate that their respective contributions to, receptor-ligand complex stability reside mostly in their different, contributions to solvation/desolvation. Together, the data demonstrate the, critical role of ligand desolvation in determining binding affinity, with, general implications for the binding of hormones to their cognate nuclear, receptors.

 

==About this Structure==

2R40 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Heliothis_virescens Heliothis virescens] with <scene name='pdbligand=FLC:'>FLC</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=20E:'>20E</scene>, <scene name='pdbligand=EPH:'>EPH</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R40 OCA].

 

==Reference==

Critical Role of Desolvation in the Binding of 20-Hydroxyecdysone to the Ecdysone Receptor., Browning C, Martin E, Loch C, Wurtz JM, Moras D, Stote RH, Dejaegere AP, Billas IM, J Biol Chem. 2007 Nov 9;282(45):32924-32934. Epub 2007 Sep 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17848566 17848566]

[[Category: Protein complex]]

[[Category: Billas, I.M.L.]]

[[Category: Browning, C.]]

[[Category: Moras, D.]]