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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

-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

When the protein is colored according to , residues at the ligand site are the most conserved.

Interactions that stabilize ligand binding^[1] include hydrogen bonding from Tyr149 and Gln152 backbone carbonyls and Thr154 sidechain OH to the and hydrogen bonding from the sidechain nitrogens of Arg64, Arg69, and Arg73 to the two .

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

When the protein is colored according to , residues at the ligand site are the most conserved.

Interactions that stabilize ligand binding^[2] include hydrogen bonding from Tyr149 and Gln152 backbone carbonyls and Thr154 sidechain OH to the and hydrogen bonding from the sidechain nitrogens of Arg64, Arg69, and Arg73 to the two .

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

2. Difference that can be observed from GSK-3 beta complexes with Staurosporine and other inhibitors (AMP-PNP, indirubin-3'-monoxime)

Quiz Question 1

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

Quiz Question 2

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

Drug Binding Site - Christina Lincoln

Additional Features - Bach Pham & Elvan Cevac

Quiz Question 1 - Nerses Haroutunian

Quiz Question 2 - Nick H-K

References

1. ↑ Milburn MV, Prive GG, Milligan DL, Scott WG, Yeh J, Jancarik J, Koshland DE Jr, Kim SH. Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand. Science. 1991 Nov 29;254(5036):1342-7. PMID:1660187
2. ↑ Milburn MV, Prive GG, Milligan DL, Scott WG, Yeh J, Jancarik J, Koshland DE Jr, Kim SH. Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand. Science. 1991 Nov 29;254(5036):1342-7. PMID:1660187