4jr7: Difference between revisions
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''' | ==Crystal structure of scCK2 alpha in complex with GMPPNP== | ||
<StructureSection load='4jr7' size='340' side='right' caption='[[4jr7]], [[Resolution|resolution]] 1.48Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jr7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JR7 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CKA1, YIL035C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=4jr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jr7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jr7 RCSB], [http://www.ebi.ac.uk/pdbsum/4jr7 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CK2 is a ubiquitous and conserved protein kinase in eukaryotic organisms and is important in many biological processes. It is unique in maintaining constitutive activity and in using both ATP and GTP as phosphor donors. In this study, crystal structures of recombinant Saccharomyces cerevisiae CK2alpha (scCK2alpha) complexed with GMPPNP, ATP and AMPPN with either Mg2+ or Mn2+ as the coordinated divalent cation are presented. The overall structure of scCK2alpha shows high similarity to its homologous proteins by consisting of two domains with the co-substrate lying in the cleft between them. However, three characteristic features distinguish scCK2alpha from its homologues. Firstly, the Lys45-Glu53 and Arg48-Glu53 interactions in scCK2alpha lead Lys50 to adopt a unique conformation that is able to stabilize the gamma-phosphate of the co-substrate, which makes the existence of the `essential divalent cation' not so essential. The multiple nucleotide-divalent cation binding modes of the active site of scCK2alpha are apparently different from the two-divalent-cation-occupied active site of Zea mays CK2alpha and human CK2alpha. Secondly, conformational change of Glu53 in scCK2alpha-AMPPN breaks its interaction with Lys45 and Arg48; as a result, the co-substrate binding pocket becomes more open. This may suggest a clue to a possible ADP/GDP-release pathway, because the NE1 atom of the Trp in the `DWG motif' of CK2alpha forms a hydrogen bond to the O atom of Leu212, which seems to make ADP release by means of the `DFG-in flip to DFG-out' model found in most eukaryotic protein kinases impossible. Coincidentally, two sulfate ions which may mimic two phosphate groups were captured by Arg161 and Lys197 around the pocket. Mutagenesis and biochemical experiments on R161A and K197A mutants support the above proposal. Finally, scCK2alpha is unique in containing an insertion region whose function had not been identified in previous research. It is found that the insertion region contributes to maintaining the constitutively active conformation of the scCK2alpha catalytic site, but does not participate in interaction with the regulatory subunits. | |||
The | The multiple nucleotide-divalent cation binding modes of Saccharomyces cerevisiae CK2alpha indicate a possible co-substrate hydrolysis product (ADP/GDP) release pathway.,Liu H, Wang H, Teng M, Li X Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):501-13. doi:, 10.1107/S1399004713027879. Epub 2014 Jan 30. PMID:24531484<ref>PMID:24531484</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Baker's yeast]] | |||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Liu, H.]] | |||
[[Category: Protein kinase]] | |||
[[Category: Protein phosphorylation]] | |||
[[Category: Transferase]] | |||
Revision as of 15:10, 18 May 2014
Crystal structure of scCK2 alpha in complex with GMPPNPCrystal structure of scCK2 alpha in complex with GMPPNP
Structural highlights
Publication Abstract from PubMedCK2 is a ubiquitous and conserved protein kinase in eukaryotic organisms and is important in many biological processes. It is unique in maintaining constitutive activity and in using both ATP and GTP as phosphor donors. In this study, crystal structures of recombinant Saccharomyces cerevisiae CK2alpha (scCK2alpha) complexed with GMPPNP, ATP and AMPPN with either Mg2+ or Mn2+ as the coordinated divalent cation are presented. The overall structure of scCK2alpha shows high similarity to its homologous proteins by consisting of two domains with the co-substrate lying in the cleft between them. However, three characteristic features distinguish scCK2alpha from its homologues. Firstly, the Lys45-Glu53 and Arg48-Glu53 interactions in scCK2alpha lead Lys50 to adopt a unique conformation that is able to stabilize the gamma-phosphate of the co-substrate, which makes the existence of the `essential divalent cation' not so essential. The multiple nucleotide-divalent cation binding modes of the active site of scCK2alpha are apparently different from the two-divalent-cation-occupied active site of Zea mays CK2alpha and human CK2alpha. Secondly, conformational change of Glu53 in scCK2alpha-AMPPN breaks its interaction with Lys45 and Arg48; as a result, the co-substrate binding pocket becomes more open. This may suggest a clue to a possible ADP/GDP-release pathway, because the NE1 atom of the Trp in the `DWG motif' of CK2alpha forms a hydrogen bond to the O atom of Leu212, which seems to make ADP release by means of the `DFG-in flip to DFG-out' model found in most eukaryotic protein kinases impossible. Coincidentally, two sulfate ions which may mimic two phosphate groups were captured by Arg161 and Lys197 around the pocket. Mutagenesis and biochemical experiments on R161A and K197A mutants support the above proposal. Finally, scCK2alpha is unique in containing an insertion region whose function had not been identified in previous research. It is found that the insertion region contributes to maintaining the constitutively active conformation of the scCK2alpha catalytic site, but does not participate in interaction with the regulatory subunits. The multiple nucleotide-divalent cation binding modes of Saccharomyces cerevisiae CK2alpha indicate a possible co-substrate hydrolysis product (ADP/GDP) release pathway.,Liu H, Wang H, Teng M, Li X Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):501-13. doi:, 10.1107/S1399004713027879. Epub 2014 Jan 30. PMID:24531484[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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