2phk
From Proteopedia
(New page: 200px<br /><applet load="2phk" size="450" color="white" frame="true" align="right" spinBox="true" caption="2phk, resolution 2.6Å" /> '''THE CRYSTAL STRUCTURE...) |
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| - | [[Image:2phk.jpg|left|200px]]<br /><applet load="2phk" size=" | + | [[Image:2phk.jpg|left|200px]]<br /><applet load="2phk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2phk, resolution 2.6Å" /> | caption="2phk, resolution 2.6Å" /> | ||
'''THE CRYSTAL STRUCTURE OF A PHOSPHORYLASE KINASE PEPTIDE SUBSTRATE COMPLEX: KINASE SUBSTRATE RECOGNITION'''<br /> | '''THE CRYSTAL STRUCTURE OF A PHOSPHORYLASE KINASE PEPTIDE SUBSTRATE COMPLEX: KINASE SUBSTRATE RECOGNITION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of a truncated form of the gamma-subunit of phosphorylase | + | The structure of a truncated form of the gamma-subunit of phosphorylase kinase (PHKgammat) has been solved in a ternary complex with a non-hydrolysable ATP analogue (adenylyl imidodiphosphate, AMPPNP) and a heptapeptide substrate related in sequence to both the natural substrate and to the optimal peptide substrate. Kinetic characterization of the phosphotransfer reaction confirms the peptide to be a good substrate, and the structure allows identification of key features responsible for its high affinity. Unexpectedly, the substrate peptide forms a short anti-parallel beta-sheet with the kinase activation segment, the region which in other kinases plays an important role in regulation of enzyme activity. This anchoring of the main chain of the substrate peptide at a fixed distance from the gamma-phosphate of ATP explains the selectivity of PHK for serine/threonine over tyrosine as a substrate. The catalytic core of PHK exists as a dimer in crystals of the ternary complex, and the relevance of this phenomenon to its in vivo recognition of dimeric glycogen phosphorylase b is considered. |
==About this Structure== | ==About this Structure== | ||
| - | 2PHK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with MN, ATP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase_kinase Phosphorylase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.19 2.7.11.19] Full crystallographic information is available from [http:// | + | 2PHK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase_kinase Phosphorylase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.19 2.7.11.19] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PHK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phosphorylase kinase]] | [[Category: Phosphorylase kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Johnson, L | + | [[Category: Johnson, L N.]] |
| - | [[Category: Lowe, E | + | [[Category: Lowe, E D.]] |
| - | [[Category: Noble, M | + | [[Category: Noble, M E.M.]] |
| - | [[Category: Oikonomakos, N | + | [[Category: Oikonomakos, N G.]] |
| - | [[Category: Owen, D | + | [[Category: Owen, D J.]] |
| - | [[Category: Skamnaki, V | + | [[Category: Skamnaki, V T.]] |
[[Category: ATP]] | [[Category: ATP]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: substrate recognition]] | [[Category: substrate recognition]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:29:30 2008'' |
Revision as of 16:29, 21 February 2008
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THE CRYSTAL STRUCTURE OF A PHOSPHORYLASE KINASE PEPTIDE SUBSTRATE COMPLEX: KINASE SUBSTRATE RECOGNITION
Overview
The structure of a truncated form of the gamma-subunit of phosphorylase kinase (PHKgammat) has been solved in a ternary complex with a non-hydrolysable ATP analogue (adenylyl imidodiphosphate, AMPPNP) and a heptapeptide substrate related in sequence to both the natural substrate and to the optimal peptide substrate. Kinetic characterization of the phosphotransfer reaction confirms the peptide to be a good substrate, and the structure allows identification of key features responsible for its high affinity. Unexpectedly, the substrate peptide forms a short anti-parallel beta-sheet with the kinase activation segment, the region which in other kinases plays an important role in regulation of enzyme activity. This anchoring of the main chain of the substrate peptide at a fixed distance from the gamma-phosphate of ATP explains the selectivity of PHK for serine/threonine over tyrosine as a substrate. The catalytic core of PHK exists as a dimer in crystals of the ternary complex, and the relevance of this phenomenon to its in vivo recognition of dimeric glycogen phosphorylase b is considered.
About this Structure
2PHK is a Single protein structure of sequence from Oryctolagus cuniculus with , and as ligands. Active as Phosphorylase kinase, with EC number 2.7.11.19 Full crystallographic information is available from OCA.
Reference
The crystal structure of a phosphorylase kinase peptide substrate complex: kinase substrate recognition., Lowe ED, Noble ME, Skamnaki VT, Oikonomakos NG, Owen DJ, Johnson LN, EMBO J. 1997 Nov 17;16(22):6646-58. PMID:9362479
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Categories: Oryctolagus cuniculus | Phosphorylase kinase | Single protein | Johnson, L N. | Lowe, E D. | Noble, M E.M. | Oikonomakos, N G. | Owen, D J. | Skamnaki, V T. | ATP | GOL | MN | Catalytic mechanism | Complex (transferase/peptide) | Dimerization | Reversible phosphorylisation | Substrate recognition
