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	General Overview (alpha-beta arrangements, number of strands etc.)		General Overview (alpha-beta arrangements, number of strands etc.)
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		+	polymerization binding site
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		+	peptide anchor
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		+	design of polymerization inhibitors?

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Revision as of 22:24, 5 March 2012

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 1 YourMacromolecule 1.1 Introduction 1.2 Overall Structure 1.3 Binding Interactions 1.4 Additional Features 1.5 Credits 1.6 References

YourMacromolecule

Introduction

spinqualitylabelsall models Test Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Overall Structure

General Overview (alpha-beta arrangements, number of strands etc.)

polymerization binding site

peptide anchor

design of polymerization inhibitors?

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

References