Sandbox Reserved 433

This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439.

Estrogen receptor beta/p-hydroxybenzene sulfonamide complexes (2yly)

by Benjamin Homyak, Soo Lim Park, Marissa Burgess

Student Projects for UMass Chemistry 423 Spring 2016 <StructureSection load='2yly' size='350' side='right' caption='caption for Molecular Playground (PDB entry 2yly)' scene=>

Introduction

- Estrogen Receptor 2 beta/p-hydroxybenzene sulfonamide complexes

- A series of p-hydroxybenzenesulphonamides ERb receptor agonists were discovered and several compounds identified had excellent selectivity over the related ERa receptor. One of these, compound 11, had an interesting binding conformation determined by X-ray and represents an excellent starting point in the quest for further selective ERb agonists.

- There has been significant interest in the potential therapeutic benefit of selective ERb agonists to treat a variety of conditions including endometriosis3 and inflammatory bowel disease

- The amino acid sequence of the ligand binding domains between ERa and ERb is very highly conserved with only minor differences; Leu384 and Met421 in ERa is replaced by Met336 and Ile373 in ERb. The overall molecule is shown here with the Met336 and Ile373 in ERb in blue to show their location.

1. The amines were either purchased commercially or made via addition of a primary amine to an epoxide as shown in Scheme 2. The compounds were tested as racemates and those of interest were separated by chiral HPLC. A wide range of analogues were prepared utilising the approach described.

This is an overall scene with the beta sheets in purple and the alpha helices in ball and stick figures Overall Structure

Here is another scene with a rainbow diagram description of the whole protein Rainbow diagram

Overall Structure

Initial Scene

Secondary Structure -(alpha helices and beta sheets, insert green scenes here of each)

Polar and Nonpolar Groups -(green scene of polar coloring and nonpolar coloring here) -surface groups vs. buried groups

Binding Interactions

Soo Lim put your stuff here

See Also

• [Estrogen Receptor]
• [1yy4]
• [1u3s]
• [1x78]
• [1qkn]

Credits

Introduction - Benjamin Homyak

Overall Structure - Marissa Burgess

Drug Binding Site - Soo Lim Park