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https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Michael+Purol Proteopedia - User contributions [en] 2026-09-19T03:52:20Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012790 Michael Purol Sandbox 1 2009-11-03T16:15:50Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). [1] In human osteosarcomas, p19INK4d function has been found to be altered by phosphorylation at Ser 66 and Ser 76 and ubiquitination at Lys 62. [5]<br /> <br /> ==Cancer Prevention==<br /> <br /> In a 2005 study by Ceruti et al., researchers determined that in addition to and perhaps even independent of its role as a cell cycle inhibitor, p19INK4d is involved in the maintenence of DNA integrity and, therefore, would contribute to cancer prevention. [3] This study shows that p19INK4d is the only INK4 protein whose expression is induced by UV light in neuroblastoma cells, and that this expression clearly reduces UV-induced (DNA-damage-induced) apoptosis by enhancing cellular ability to repair damaged DNA. [3]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that mutants with the glutamate substitutions at Ser 76, as well as mutants with glutamate substitutions at both Ser 66 and 76, were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and higher flexibility in the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to more readily access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> <br /> ==About this Structure==<br /> 1BD8 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD8 OCA]. <br /> <br /> ==References==<br /> [1] Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA. (1998). Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a). Structure with Folding & Design 6,1279-1290. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012789 Michael Purol Sandbox 1 2009-11-03T16:15:04Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). [1] In human osteosarcomas, p19INK4d function has been found to be altered by phosphorylation at Ser 66 and Ser 76 and ubiquitination at Lys 62. [5]<br /> <br /> ==Cancer Prevention==<br /> <br /> In a 2005 study by Ceruti et al., researchers determined that, in addition to, and perhaps even independent of its role as a cell cycle inhibitor, p19INK4d is involved in the maintenence of DNA integrity and, therefore, would contribute to cancer prevention. [3] This study shows that p19INK4d is the only INK4 protein whose expression is induced by UV light in neuroblastoma cells, and that this expression clearly reduces UV-induced (DNA-damage-induced) apoptosis by enhancing cellular ability to repair damaged DNA. [3]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that mutants with the glutamate substitutions at Ser 76, as well as mutants with glutamate substitutions at both Ser 66 and 76, were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and higher flexibility in the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to more readily access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> <br /> ==About this Structure==<br /> 1BD8 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD8 OCA]. <br /> <br /> ==References==<br /> [1] Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA. (1998). Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a). Structure with Folding & Design 6,1279-1290. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012783 Michael Purol Sandbox 1 2009-11-03T16:01:25Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). [1] In human osteosarcomas, p19INK4d function has been found to be altered by phosphorylation at Ser 66 and Ser 76 and ubiquitination at Lys 62. [5]<br /> <br /> ==Cancer Prevention==<br /> <br /> In a 2005 study by Ceruti et al., researchers determined that, in addition to its role as a cell cycle inhibitor, p19INK4d is involved in the maintenence of DNA integrity and, therefore, would contribute to cancer prevention. [3] This study shows that p19INK4d is the only INK4 protein whose expression is induced by UV light in neuroblastoma cells, and that this expression clearly reduces UV-induced (DNA-damage-induced) apoptosis by enhancing cellular ability to repair damaged DNA. [3]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that both mutants with the glutamate substitutions at Ser 76 only and doubly-substituted mutants with glutamate substitutions at Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and a higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> more easily and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> <br /> ==About this Structure==<br /> 1BD8 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD8 OCA]. <br /> <br /> ==References==<br /> [1] Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA. (1998). Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a). Structure with Folding & Design 6,1279-1290. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012780 Michael Purol Sandbox 1 2009-11-03T15:49:47Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). [1] In human osteosarcomas, p19INK4d function has been found to be altered by phosphorylation at Ser 66 and Ser 76 and ubiquitination at Lys 62. [5]<br /> <br /> ==Cancer Prevention==<br /> <br /> In a 2005 study by Ceruti et al., researchers determined that, in addition to and independent of its role as a cell cycle inhibitor, p19INK4d is involved in the maintenence of DNA integrity and, therefore, would contribute to cancer prevention. [3] This study shows that p19INK4d is the only INK4 protein whose expression is induced by UV light in neuroblastoma cells, and that this expression clearly reduces UV-induced (DNA-damage-induced) apoptosis by enhancing cellular ability to repair damaged DNA. [3]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that both mutants with the glutamate substitutions at Ser 76 only and doubly-substituted mutants with glutamate substitutions at Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and a higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> more easily and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> <br /> ==About this Structure==<br /> 1BD8 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD8 OCA]. <br /> <br /> ==References==<br /> [1] Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA. (1998). Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a). Structure with Folding & Design 6,1279-1290. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012777 Michael Purol Sandbox 1 2009-11-03T15:34:20Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). [1] In human osteosarcomas, p19INK4d function has been found to be altered or inhibited by phosphorylation at both Ser 66 and Ser 76, and also ubiquitinated at Lys 62. [5]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that both mutants with the glutamate substitutions at Ser 76 only and doubly-substituted mutants with glutamate substitutions at Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and a higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> more easily and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==About this Structure==<br /> 1BD8 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BD8 OCA]. <br /> <br /> ==References==<br /> [1] Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA. (1998). Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a). Structure with Folding & Design 6,1279-1290. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012775 Michael Purol Sandbox 1 2009-11-03T15:31:01Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). [1] In human osteosarcomas, p19INK4d function has been found to be altered or inhibited by phosphorylation at both Ser 66 and Ser 76, and also ubiquitinated at Lys 62. [5]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that both mutants with the glutamate substitutions at Ser 76 only and doubly-substituted mutants with glutamate substitutions at Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and a higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> more easily and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==References==<br /> [1] Baumgartner R, Fernandez-Catalan C, Winoto A, Huber R, Engh RA, Holak TA. (1998). Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a). Structure with Folding & Design 6,1279-1290. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012762 Michael Purol Sandbox 1 2009-11-03T14:59:38Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene>, and Ubiquitination ligase has been found to attack the <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> position. [4]<br /> <br /> <br /> ==Cancer==<br /> <br /> In human osteosarcomas, p19INK4d function has been found to be altered or inhibited by phosphorylation at both Ser 66 and Ser 76, and also ubiquitinated at Lys 62. [5]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that both mutants with the glutamate substitutions at Ser 76 only and doubly-substituted mutants with glutamate substitutions at Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and a higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> more easily and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012761 Michael Purol Sandbox 1 2009-11-03T14:57:25Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). The binding interactions between p19INK4d and CDK4/6 occur primarily at AR 1 and AR2. Phosphorylation sites of p19INK4d have been identified at Ser 66 and Ser 76, and Ubiquitination ligase has been found to attack the Lys 62 position. <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> ==Cancer==<br /> <br /> In human osteosarcomas, p19INK4d function has been found to be altered or inhibited by phosphorylation at both Ser 66 and Ser 76, and also ubiquitinated at Lys 62. [5]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that both mutants with the glutamate substitutions at Ser 76 only and doubly-substituted mutants with glutamate substitutions at Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to a partial unfolding reaction and a higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene> more easily and thus tag p19INK4d for degradation at the proteasome. [4] <br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012738 Michael Purol Sandbox 1 2009-11-03T14:37:17Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> ==Cancer==<br /> <br /> In human osteosarcomas, p19INK4d function has been found to be altered or inhibited by phosphorylation at both Ser 66 and Ser 76, and also ubiquitinated at Lys 62. [5]<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. Results indicated that mutants with the glutamate substitutions at Ser 76 by itself, and mutants with glutamate substitutions at both Ser 66 and 76 were significantly destabilized in comparison to the wild-type protein, while mutants with only a Ser 66 glutamate substitution showed no significant destabilization. In particular, the results supported earlier findings that a negative charge at Ser 76 severely decreases protein stability in AR1 and AR2 by affecting the hydrogen bonding pattern of the adjacent residues, leading to higher flexibility of the loop. These findings suggest that phosphorylation or mimetic mutation at Ser 76 position allows ubiquitin ligase to access Lys 62 more easily and thus tag p19 for degradation at the proteasome. [4] <br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012729 Michael Purol Sandbox 1 2009-11-03T14:24:38Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> ==Cancer==<br /> <br /> In human osteosarcomas, p19INK4d has been found to phosphorylated at both Ser 66 and Ser 76, and also ubiquitinated at Lys 62. <br /> <br /> ==Low et al. (2009) Study==<br /> <br /> This study took an in-depth look at the structural consequences of phosphorylation at different sites of p19INK4d. Low et al. replaced Phe 86 with a trytophan residue which acted as a fluorescence-sensitive probe within a pseudo-wild type (in stability and function) mutant that displayed a hyperfluorescent intermediate which could be detected in unfolding and folding kinetics, but not at equilibrium conditions.<br /> <br /> Researchers then mimicked known phosphorylation sites with glutamate substitutions at <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene> and <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene> within ''E. coli'' to test the impact of introduced negative charges at these positions on the structural stability of P19INK4d. <br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012723 Michael Purol Sandbox 1 2009-11-03T13:45:07Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> ==Cancer==<br /> <br /> ==Low et al. (2009) Study==<br /> <br /> ==Ceruti et al. (2005) Study==<br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012722 Michael Purol Sandbox 1 2009-11-03T13:42:56Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19INK4d in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> ==p19INK4d Structure==<br /> <br /> The four INK4 proteins share a similar sturcture consisting of either four (p15 & p16) or five (p18 and '''p19''') ankyrin repeats (AR). <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> ==Cancer==<br /> <br /> <br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012717 Michael Purol Sandbox 1 2009-11-03T13:25:34Z

<p>Michael Purol: </p> <hr /> <div>===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19 in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors, which includes p16INK4a, p15INK4b,and p18INK4c. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase. The INK4 family members specifically bind to CDK4 and CDK6, inhibiting cyclin-CDK complexation and obstructing the progression of G1 phase. <br /> <br /> To view p19INK4d bound to CDK6, click here: <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> <br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> <br /> <br /> <br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ and others. (1998). Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell-cycle inhibitor p19(INK4d). Nature 395,244-250. <br /> <br /> [3] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [4] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [5] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012708 Michael Purol Sandbox 1 2009-11-03T12:55:11Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19 in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase.<br /> <br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene><br /> <br /> <br /> <br /> ==References==<br /> [1] Barrick D. (2009). Biological Regulation via Ankyrin Repeat Folding. Acs Chemical Biology 4,19-22. <br /> <br /> [2] Ceruti JM, Scassa ME, Flo JM, Varone CL, Canepa ET. (2005). Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene 24,4065-4080. <br /> <br /> [3] Low C, Homeyer N, Weininger U, Sticht H, Balbach J. (2009). Conformational Switch upon Phosphorylation: Human CDK Inhibitor p19(INK4d) between the Native and Partially Folded State. Acs Chemical Biology 4,53-63. <br /> <br /> [4] Thullberg M, Bartek J, Lukas J. (2000). Ubiquitin/proteasome-mediated degradation of p19(INK4d) determines its periodic expression during the cell cycle. Oncogene 19,2870-2876.</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012707 Michael Purol Sandbox 1 2009-11-03T12:43:15Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==p19 in the Cell Cycle==<br /> <br /> CDK Inhibitor p19INK4d is a cyclin-dependent kinase (CDK) inhibitor in the INK4 family of CDK inhibitors. Progression through the G1 phase of the cell cycle and subsequent entry into the S phase depend on the phosphorylating effects of CDK4 and CDK6. These two CDKs must form cyclin-CDK complexes to phosphorylate the retinoblastoma protein, inhibiting its growth-suppressing function, and triggering an E2F-dependent transcriptional program necessary for entry into S phase.<br /> <br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012698 Michael Purol Sandbox 1 2009-11-03T07:53:50Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> CDK Inhibitor p19INK4d is a Cyclin-Dependent Kinase (CDK) Inhibitor in the INK4 family of CDK inhibitors. The INK4 CDK inhibitors bind and inhibit CDK4 and CDK6, the two cyclin-dependent kinases involved in the progression through the G1 phase of the cell cycle.<br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012697 Michael Purol Sandbox 1 2009-11-03T06:18:33Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)<br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Cdk6-p19ink4d_inhibitor_compl/1'>CDK6-p19INK4d inhibitor complex</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012696 Michael Purol Sandbox 1 2009-11-03T05:58:08Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)<br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_76/1'>Ser 76</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012695 Michael Purol Sandbox 1 2009-11-03T05:49:34Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)<br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Ser_66/1'>Ser 66</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012687 Michael Purol Sandbox 1 2009-11-03T05:28:42Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)<br /> <br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012686 Michael Purol Sandbox 1 2009-11-03T05:28:03Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)<br /> <br /> <scene name='Michael_Purol_Sandbox_1/P19ink4d/2'>Lys 62</scene><br /> <br /> <scene name='Michael_Purol_Sandbox_1/Lys_62/1'>Lys 62</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012684 Michael Purol Sandbox 1 2009-11-03T05:24:27Z

<p>Michael Purol: LYS 62</p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)<br /> <br /> <scene name='Michael_Purol_Sandbox_1/P19ink4d/2'>Lys 62</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=1012659 Michael Purol Sandbox 1 2009-11-03T04:25:25Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> <br /> <br /> ===CDK Inhibitor p19INK4d===<br /> <br /> [[Image:1bd8.png|left|200px]]<br /> <br /> {{STRUCTURE_1bd8 | PDB= 1bd8 | SCENE= }}<br /> <br /> ==Overview of p19==<br /> <br /> The <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>following sites</scene> are ubquitinated (green) or phosphorylated (red)</div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=998816 Michael Purol Sandbox 1 2009-09-22T14:34:39Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load <br /> and display another structure.<br /> <br /> {{STRUCTURE_1BD8 | PDB=1BD8 | SCENE= }}<br /> <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>CDK Inhibitor p19INK4d</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=998783 Michael Purol Sandbox 1 2009-09-22T02:56:33Z

<p>Michael Purol: </p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load <br /> and display another structure.<br /> <br /> {{STRUCTURE_3cin | PDB=3cin | SCENE= }}<br /> <scene name='Michael_Purol_Sandbox_1/P19ink4d/1'>CDK Inhibitor p19INK4d</scene></div>

Michael Purol https://proteopedia.org/index.php?title=Michael_Purol_Sandbox_1&diff=998782 Michael Purol Sandbox 1 2009-09-22T02:38:31Z

<p>Michael Purol: New page: ==This is a placeholder== This is a placeholder text to help you get started in placing a Jmol applet on your page. At any time, click "Show Preview" at the bottom of this page to see how...</p> <hr /> <div>==This is a placeholder==<br /> This is a placeholder text to help you get started in <br /> placing a Jmol applet on your page. At any time, click<br /> "Show Preview" at the bottom of this page to see how it goes.<br /> <br /> Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load <br /> and display another structure.<br /> <br /> {{STRUCTURE_3cin | PDB=3cin | SCENE= }}</div>

Michael Purol