2biy
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 3-Phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates the, T-loop of several AGC (cAMP-dependent, cGMP-dependent, protein kinase C), family protein kinases, resulting in their activation. Previous structural, studies have revealed that the alpha C-helix, located in the small lobe of, the kinase domain of PDK1, is a key regulatory element, as it links a, substrate interacting site termed the hydrophobic motif (HM) pocket with, the phosphorylated Ser-241 in the T-loop. In this study we have, demonstrated by mutational analysis that interactions between the, phosphorylated Ser-241 and the alpha C-helix are not required for PDK1, activity or substrate binding through the HM-pocket but are necessary for, PDK1 to be activated or stabilized by a peptide that binds to this site., ... | + | 3-Phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates the, T-loop of several AGC (cAMP-dependent, cGMP-dependent, protein kinase C), family protein kinases, resulting in their activation. Previous structural, studies have revealed that the alpha C-helix, located in the small lobe of, the kinase domain of PDK1, is a key regulatory element, as it links a, substrate interacting site termed the hydrophobic motif (HM) pocket with, the phosphorylated Ser-241 in the T-loop. In this study we have, demonstrated by mutational analysis that interactions between the, phosphorylated Ser-241 and the alpha C-helix are not required for PDK1, activity or substrate binding through the HM-pocket but are necessary for, PDK1 to be activated or stabilized by a peptide that binds to this site., The structure of an inactive T-loop mutant of PDK1, in which Ser-241 is, changed to Ala, was also determined. This structure, together with surface, plasmon resonance binding studies, demonstrates that the, PDK1(S241A)-inactive mutant possesses an intact HM-pocket as well as an, ordered alpha C-helix. These findings reveal that the integrity of the, alpha C-helix and HM-pocket in PDK1 is not regulated by T-loop, phosphorylation. |
==About this Structure== | ==About this Structure== | ||
| - | 2BIY is a | + | 2BIY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, ATP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Structure known Active Site: BC6. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BIY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:22:26 2007'' |
Revision as of 13:17, 5 November 2007
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STRUCTURE OF PDK1-S241A MUTANT KINASE DOMAIN
Overview
3-Phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates the, T-loop of several AGC (cAMP-dependent, cGMP-dependent, protein kinase C), family protein kinases, resulting in their activation. Previous structural, studies have revealed that the alpha C-helix, located in the small lobe of, the kinase domain of PDK1, is a key regulatory element, as it links a, substrate interacting site termed the hydrophobic motif (HM) pocket with, the phosphorylated Ser-241 in the T-loop. In this study we have, demonstrated by mutational analysis that interactions between the, phosphorylated Ser-241 and the alpha C-helix are not required for PDK1, activity or substrate binding through the HM-pocket but are necessary for, PDK1 to be activated or stabilized by a peptide that binds to this site., The structure of an inactive T-loop mutant of PDK1, in which Ser-241 is, changed to Ala, was also determined. This structure, together with surface, plasmon resonance binding studies, demonstrates that the, PDK1(S241A)-inactive mutant possesses an intact HM-pocket as well as an, ordered alpha C-helix. These findings reveal that the integrity of the, alpha C-helix and HM-pocket in PDK1 is not regulated by T-loop, phosphorylation.
About this Structure
2BIY is a Single protein structure of sequence from Homo sapiens with SO4, ATP and GOL as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Structure known Active Site: BC6. Full crystallographic information is available from OCA.
Reference
Role of T-loop phosphorylation in PDK1 activation, stability, and substrate binding., Komander D, Kular G, Deak M, Alessi DR, van Aalten DM, J Biol Chem. 2005 May 13;280(19):18797-802. Epub 2005 Mar 1. PMID:15741170
Page seeded by OCA on Mon Nov 5 15:22:26 2007
Categories: Homo sapiens | Single protein | Transferred entry: 2.7.11.1 | Aalten, D.M.F.Van. | Alessi, D.R. | Deak, M. | Komander, D. | Kular, G.S. | ATP | GOL | SO4 | Ac-helix | Agc kinase | Atp-binding | Phosphoinositide dependent protein kinase | Phosphorylation | Pi3-kinase signalling | Pif-pocket | Pka | Pkb | Serine-threonine-protein kinase | T-loop mutant | Transferase
