2hw6: Difference between revisions

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[[Image:2hw6.png|left|200px]]
==Crystal structure of Mnk1 catalytic domain==
<StructureSection load='2hw6' size='340' side='right' caption='[[2hw6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hw6]] is a 2 chain structure with 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=2HW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HW6 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ac3|2ac3]], [[2ac5|2ac5]], [[2hw7|2hw7]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MKNK1, MNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hw6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2hw6 PDBsum]</span></td></tr>
<table>
== 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/hw/2hw6_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Autoinhibition is a recurring mode of protein kinase regulation and can be based on diverse molecular mechanisms. Here, we show by crystal structure analysis, nuclear magnetic resonance (NMR)-based nucleotide affinity studies and rational mutagenesis that nonphosphorylated mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1 is autoinhibited by conversion of the activation segment into an autoinhibitory module. In a Mnk1 crystal structure, the activation segment is repositioned via a Mnk-specific sequence insertion at the N-terminal lobe with the following consequences: (i) the peptide substrate binding site is deconstructed, (ii) the interlobal cleft is narrowed, (iii) an essential Lys-Glu pair is disrupted and (iv) the magnesium-binding loop is locked into an ATP-competitive conformation. Consistently, deletion of the Mnk-specific insertion or removal of a conserved phenylalanine side chain, which induces a blockade of the ATP pocket, increase the ATP affinity of Mnk1. Structural rearrangements required for the activation of Mnks are apparent from the cocrystal structure of a Mnk2 D228G -staurosporine complex and can be modeled on the basis of crystal packing interactions. Our data suggest a novel regulatory mechanism specific for the Mnk subfamily.


{{STRUCTURE_2hw6|  PDB=2hw6  |  SCENE=  }}
Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.,Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. PMID:16917500<ref>PMID:16917500</ref>


===Crystal structure of Mnk1 catalytic domain===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


{{ABSTRACT_PUBMED_16917500}}
==See Also==
 
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
==About this Structure==
== References ==
[[2hw6]] is a 2 chain structure with 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=2HW6 OCA].
<references/>
 
__TOC__
==Reference==
</StructureSection>
<ref group="xtra">PMID:016917500</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 10:45, 30 September 2014

Crystal structure of Mnk1 catalytic domainCrystal structure of Mnk1 catalytic domain

Structural highlights

2hw6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:2ac3, 2ac5, 2hw7
Gene:MKNK1, MNK1 (Homo sapiens)
Activity:Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:FirstGlance, OCA, RCSB, PDBsum

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 PubMed

Autoinhibition is a recurring mode of protein kinase regulation and can be based on diverse molecular mechanisms. Here, we show by crystal structure analysis, nuclear magnetic resonance (NMR)-based nucleotide affinity studies and rational mutagenesis that nonphosphorylated mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1 is autoinhibited by conversion of the activation segment into an autoinhibitory module. In a Mnk1 crystal structure, the activation segment is repositioned via a Mnk-specific sequence insertion at the N-terminal lobe with the following consequences: (i) the peptide substrate binding site is deconstructed, (ii) the interlobal cleft is narrowed, (iii) an essential Lys-Glu pair is disrupted and (iv) the magnesium-binding loop is locked into an ATP-competitive conformation. Consistently, deletion of the Mnk-specific insertion or removal of a conserved phenylalanine side chain, which induces a blockade of the ATP pocket, increase the ATP affinity of Mnk1. Structural rearrangements required for the activation of Mnks are apparent from the cocrystal structure of a Mnk2 D228G -staurosporine complex and can be modeled on the basis of crystal packing interactions. Our data suggest a novel regulatory mechanism specific for the Mnk subfamily.

Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.,Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. PMID:16917500[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Jauch R, Cho MK, Jakel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jackle H, Wahl MC. Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment. EMBO J. 2006 Sep 6;25(17):4020-32. Epub 2006 Aug 17. PMID:16917500

2hw6, resolution 2.50Å

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