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
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
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?
What kind of bond would GSK-3B form with a staurosporine complex? Picture is shown below.
Media:http://upload.wikimedia.org/wikipedia/commons/3/34/Staurosporine1.png
Excerpt from GSK-3: Functional Insights from Cell Biology and Animal Models:
"In certain cell types of the brain, alternative splicing between exon 8 and 9 of GSK-3β leads to the generation of an additional “long” form containing a 13 amino acid insert within the catalytic domain (GSK-3β2; see Figure Figure1).1). This insert is located between residues 303 and 304 of GSK-3β, and is flanked by two proximal α-helices of kinase subdomains X and XI (Hanks and Hunter, 1995; Mukai et al., 2002). This alternatively spliced isoform of GSK-3β in rodents (Mukai et al., 2002; Yao et al., 2002) and in human (Lau et al., 1999; Schaffer et al., 2003; Kwok et al., 2005) has been implicated in neuronal-specific functions. The short form of GSK-3β is ubiquitously expressed in the body, including the developing and adult nervous system (Takahashi et al., 1994; Leroy and Brion, 1999). By contrast, GSK-3β2 is predominantly expressed in the neural tissues, with highest levels in the developing brain and persistence into adulthood (Mukai et al., 2002; Wood-Kaczmar et al., 2009)."
"From the crystal structure, it has been proposed that unphosphorylated Tyr276/Tyr216 act to block the access of primed substrates (as discussed below). Indeed, the structure of phosphorylated GSK-3β (Bax et al., 2001) shows that phosphorylated Tyr216 undergoes a conformational change that allows substrates to bind the enzyme"
Quiz Question 2
See Also
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
