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Introduction

This is a sample scene created with SAT to by Group, and another to make of the protein.

Overall Structure

This is a sample scene created with SAT to by Group, and another to make of the protein.

-Monomer

-Glycogen Synthase Kinase-3 (GSK-3) is a serine/threonine protein kinase

-2 isoforms: alpha and beta, that are 97% homologous in their catalytic domain, but diverse at the N and C terminus.

-Both isoforms have a conserved N-terminal serine reside (S21 for alpha and S9 for beta)

-Phosphorylation of the N-terminal serine residue plays an important role for further activity

Mishra, Nibha et al. Structure based virtual screening of GSK-3beta: Importance of protein flexibility and induced fit, 2009. Bioorganic & Medicinal Chemistry Letters, 2009, Vol. 19 Iss. 19, pp. 5582-5585. Retreived from http://www.sciencedirect.com/science/article/pii/S0960894X09011780

Binding Interactions

1)Folding of protein

  a) location and description of position of alpha and beta sheets (Show in separate color on green screen)
  b) crystal structure data (Table 1, Structural Characterizaiton of the GSK-3B Active Site Using Selective and Non-selective ATP-mimetic Inhibitors)

2)Substrate binding

  a)  “phosphate-binding” pocket: describe three crucial basic residues (Show in different color on green screen)
  b)  GSK-3 substrates and binding specifics- S/TxxxS/T (S=Serine, T=threonine, X= any amino acid)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217193/ http://www.rcsb.org/pdb/explore/explore.do?pdbId=1Q3D

Additional Features

1. Difference that can be observed from complexes of Staurosporine with GSK-3 beta and other protein kinases such as CDK2, Chk1, Lck and PKA

+ In GSK-3 beta complex with Staurosporine, water is a part of a hydrogen-bonding network

+ Only direct hydrogen bonds are observed between GSK-3 beta and Staurosporine

2. Comparison of GSK-3 beta complexes with Staurosporine and other inhibitors (AMP-PNP, indirubin-3'-monoxime)

+ Between GSK-3 beta complex with Stauroporine and AMP-PNP, the position of N-terminal domain varies.

+ The angle of binding in the active site are different

+ Water is also used as intermediate in hydrogen bonding in GSK-3 beta complex with Indirubin-3'-monoxime (same with complex in Staurosporine )

http://www.sciencedirect.com.silk.library.umass.edu/science/article/pii/S0022283603010593

Quiz Question 1

Which isoform of GSK-3 would work best for ___ function in ___ pathway?

What type of bonding would GSK-3B exhibit with Staurosporine? A picture of the Staurosporine molecule is found below.

The green screen above may help you as well.

Answer: hydrogen bonding

Quiz Question 2

What are the locations of the active sites with respect to the two isoforms?

this green screen may give you a hint.

Answer: At the N and C terminal lobes.

J.A. Bertrand, S. Thieffine, A. Vulpetti, C. Cristiani, B. Valsasina, S. Knapp, H.M. Kalisz, M. Flocco, Structural Characterization of the GSK-3β Active Site Using Selective and Non-selective ATP-mimetic Inhibitors, Journal of Molecular Biology, Volume 333, Issue 2, 17 October 2003, Pages 393-407, ISSN 0022-2836, http://dx.doi.org/10.1016/j.jmb.2003.08.031.

(http://www.sciencedirect.com/science/article/pii/S0022283603010593)

See Also

• UvrABC
• Glycogen Synthase Kinase 3
• Serine/Threonie Protein Kinase
• Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d
• Glycogen Synthase Kinase 3 Beta complexed with AMP-PNP
• Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Leucettine L4
• Glycogen Synthase Kinase 3 beta (GSK3B) complexed with a ruthenium octasporine ligand (OS1)

Credits

Introduction - Zachary Plourde

Overall Structure - Sarah Johnson

Binding Interactions - Christina Lincoln

Additional Features - Bach Pham & Elvan Cevac

Quiz Question 1 - Nerses Haroutunian

Quiz Question 2 - Nick H-K

References