Sandbox Reserved 432
From Proteopedia
| 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. |
Contents |
YourMacromolecule
Introduction
|
Overall Structure
Binding Interactions
WMDF - tetra peptide with bulky side chains
WMDF binds to P14-8 peptide-antithrombin binary complex
-Tetra peptide occupies P7-P4 vacancy -Forms 8 hydrogen bonds with adjacent residues
Methionine is at the P6 location, while phenylalanine is at P4 location
-P4 & P6 locations are very critical
-Hydrophobicity of P4 & P6 are consistent feature of effective serpin-derived peptides
-results in a shift of the connecting loop when compared to latent antithrombin
-Successfully inhibits antithrombin polymerisation
Additional Features
10 million of European decent carry Z-allele of antitrypsin
-means 50% of antitrypsin polymerises -only a concern if exeeds limit of threshold
Therapeutic Techniques
-tip equilibrium towards dissociation -use of protiens to bind to more receptive and unstable form of the protein -this can hinder/prevent oligomer formation
Found out can block with smaller peptides
-3 to 4 residues instead of 6+ -small enough to give us a model for designing mimics that are not peptides
Glycerol is a molecule that can bind like this
-binds to site critical for polymerization -although one is not enough, many can be used to block
Credits
Introduction - Kevin Dillon
Overall Structure - Max Nowak
Drug Binding Site - Kyle Reed
Additional Features - Chris Carr
