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< | ==THE CRYSTAL STRUCTURE OF A PHOSPHORYLASE KINASE PEPTIDE SUBSTRATE COMPLEX: KINASE SUBSTRATE RECOGNITION== | ||
<StructureSection load='2phk' size='340' side='right'caption='[[2phk]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2phk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PHK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PHK FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2phk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2phk OCA], [https://pdbe.org/2phk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2phk RCSB], [https://www.ebi.ac.uk/pdbsum/2phk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2phk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PHKG1_RABIT PHKG1_RABIT] Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3.<ref>PMID:8454596</ref> <ref>PMID:8999860</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ph/2phk_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2phk ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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<ref>PMID:9362479</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2phk" style="background-color:#fffaf0;"></div> | |||
== References == | |||
--> | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Johnson LN]] | |||
[[Category: Lowe ED]] | |||
[[Category: Johnson | [[Category: Noble MEM]] | ||
[[Category: Lowe | [[Category: Oikonomakos NG]] | ||
[[Category: Noble | [[Category: Owen DJ]] | ||
[[Category: Oikonomakos | [[Category: Skamnaki VT]] | ||
[[Category: Owen | |||
[[Category: Skamnaki | |||
Latest revision as of 09:46, 9 August 2023
THE CRYSTAL STRUCTURE OF A PHOSPHORYLASE KINASE PEPTIDE SUBSTRATE COMPLEX: KINASE SUBSTRATE RECOGNITIONTHE CRYSTAL STRUCTURE OF A PHOSPHORYLASE KINASE PEPTIDE SUBSTRATE COMPLEX: KINASE SUBSTRATE RECOGNITION
Structural highlights
FunctionPHKG1_RABIT Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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