Sandbox Reserved 433: Difference between revisions

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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.


GSK-3 is a serine/threonine protein kinase which regulates the addition of phosphate molecules onto serineand threonine amino acid residues. Serine/threonine protein kinases are responsible for phosphorylating the serine/threonine kinase receptors which play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development <ref>PMID: 16912193</ref>. GSK-3 has two isoforms, GSK-3 beta and GSK-3 alpha. GSK-3 beta is more involved in energy metabolism, neuronal cell development, and body pattern formation, while GSK-3 alpha has more function with WNT signaling pathways. GSK-3 beta is found in most mammals, all with similar structure and function. In experiments when GSK-3 beta was perturbed in mice, embryonic lethality during mid-gestation was demonstrated.   
Glycogen synthase kinase-3, or GSK-3, is one of the main proteins that controls the activation of glycogen synthase. GSK-3 is serine/threonine protein kinase which regulates the phosphorylation of serine and threonine molecules. Serine/threonine kinase is important for the regulation of cell proliferation, cell death, cell differentiation, and embryonic development<ref>PMID: 16912193</ref>. GSK-3 is found in two forms, GSK-3β and GSK-3α. The two forms have different functions with GSK-3 β involved in energy metabolism, neuronal cell development, and body pattern formation, while GSK-3α has more function with WNT signaling pathways, which controls cell fate. This proteopedia page will be focused on GSK-3β. The GSK-3β is found in most mammals, all with similar structure and function. In experiments when GSK-3β was perturbed in mice, embryonic lethality during gestation was demonstrated<ref>PMID: 20599907</ref>.  Recent research in regards to GSK-3β includes type II diabetes, Alzheimer's Disease, inflammation, cancer, and neurological disorders such as strokes and bipolar disorder.
GSK-3 beta has been shown to negatively regulates TGF-beta1 and Angiotensin II-mediated cellular activity through interaction with Smad3. GSK-3 beta directly interacts with Smad3, preventing its movement into the nucleolus, which don't allow it to perform cell death. This forces Angiotensin II apoptosis in cardiac myocytes<ref>PMID: 14529625</ref>. Other enzymes that this kinase interacts with are: AKAP11, AXIN1, AXIN2, AR, CTNNB1, DNM1L, MACF1 MUC1, SMAD3[ NOTCH1,NOTCH2, P53, PRKAR2A, SGK3, and TSC2<ref>PMID: 20599907</ref>. Recent research in regards to GSK-3 includes type II diabetes , Alzheimer's Disease, inflammation, cancer, and bipolar disorder. This page demonstrates a GSK-3 complex with a Staurosporine inhibitor.   
GSK-3β has been shown to interact with various enzymes including: TGF- β1, Smad3, AKAP11, AXIN1, AXIN2, AR, CTNNB1, DNM1L, MACF1 MUC1, SMAD3, NOTCH1,NOTCH2, P53, PRKAR2A, SGK3, and TSC2. This page focuses on a GSK-3β complex with a Staurosporine inhibitor.  Since ATP has a stronger affinity to binding to staurosporine than to protein kinases, the molecule acts a competitive inhibitor in regards to GSK-3β<ref name="paper">PMID: 14529625</ref>.


==Overall Structure==
==Overall Structure==
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The typical hydrogen bond (H-bond) is categorized to be between 2.2 and 4.0 Å <ref name="book">Jeffrey, George A. An introduction to hydrogen bonding; Oxford University Press: Oxford, 1997</ref>.  
The typical hydrogen bond (H-bond) is categorized to be between 2.2 and 4.0 Å <ref name="book">Jeffrey, George A. An introduction to hydrogen bonding; Oxford University Press: Oxford, 1997</ref>.  
Since many pdb files lack hydrogen atoms, a significant H-bond can be considered when donor-acceptor distance are probably 3.5 Å <ref name="book" />.   
Since many pdb files lack hydrogen atoms, a significant H-bond can be considered when donor-acceptor distance are probably 3.5 Å <ref name="book" />.   
However, the length between between Gln 185 and Strauroporine is 4.47 Å which surpasses typical H-bond distance; therefore, it forms a water mediated polar interaction between these atoms instead of direct H-bond<ref name="paper">PMID: 14529625</ref>.  
However, the length between between Gln 185 and Strauroporine is 4.47 Å which surpasses typical H-bond distance; therefore, it forms a water mediated polar interaction between these atoms instead of direct H-bond<ref name="paper"/>.  
This is a unique interaction to the GSK-3β and staurosporine complex, since other protein kinase  (e.g. CDK2, Chk1, LCK, PKA) -staurosporine complexes show direct H-bond interaction  between two moieties.  
This is a unique interaction to the GSK-3β and staurosporine complex, since other protein kinase  (e.g. CDK2, Chk1, LCK, PKA) -staurosporine complexes show direct H-bond interaction  between two moieties.  


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