2zv2

From Proteopedia

(Difference between revisions)

Revision as of 12:58, 9 February 2016

Crystal structure of human calcium/calmodulin-dependent protein kinase kinase 2, beta, CaMKK2 kinase domain in complex with STO-609

Structural highlights

2zv2 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	Calcium/calmodulin-dependent protein kinase, with EC number 2.7.11.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, TOPSAN

Function

[KKCC2_HUMAN] Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching.^[1] ^[2] ^[3] ^[4]

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

Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK) kinase (CaMKK) is a member of the CaMK cascade that mediates the response to intracellular Ca(2+) elevation. CaMKK phosphorylates and activates CaMKI and CaMKIV, which directly activate transcription factors. In this study, we determined the 2.4 A crystal structure of the catalytic kinase domain (KD) of the human CaMKK beta isoform complexed with its selective inhibitor, STO-609. The structure revealed that CaMKKbeta lacks the alphaD helix and that the equivalent region displays a hydrophobic molecular surface, which may reflect its unique substrate recognition and autoinhibition. Although CaMKKbeta lacks the activation-loop phosphorylation site, the activation loop is folded in an active-state conformation, which is stabilized by a number of interactions between amino acid residues conserved among the CaMKK isoforms. An in vitro analysis of the kinase activity confirmed the intrinsic activity of the CaMKKbeta KD. Structure and sequence analyses of the STO-609-binding site revealed amino-acid replacements that may affect the inhibitor binding. Indeed, mutagenesis demonstrated that the CaMKKbeta residue Pro274, which replaces the conserved acidic residue of other protein kinases, is an important determinant for the selective inhibition by STO-609. Therefore, the present structure provides a molecular basis for clarifying the known biochemical properties of CaMKKbeta, and for designing novel inhibitors targeting CaMKKbeta and the related protein kinases.

Crystal structure of the CA2+/calmodulin-dependent protein kinase kinase in complex with the inhibitor STO-609.,Kukimoto-Niino M, Yoshikawa S, Takagi T, Ohsawa N, Tomabechi Y, Terada T, Shirouzu M, Suzuki A, Lee S, Yamauchi T, Okada-Iwabu M, Iwabu M, Kadowaki T, Minokoshi Y, Yokoyama S J Biol Chem. 2011 Apr 19. PMID:21504895^[5]

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

References

↑ Hsu LS, Chen GD, Lee LS, Chi CW, Cheng JF, Chen JY. Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity. J Biol Chem. 2001 Aug 17;276(33):31113-23. Epub 2001 Jun 6. PMID:11395482 doi:http://dx.doi.org/10.1074/jbc.M011720200
↑ Ishikawa Y, Tokumitsu H, Inuzuka H, Murata-Hori M, Hosoya H, Kobayashi R. Identification and characterization of novel components of a Ca2+/calmodulin-dependent protein kinase cascade in HeLa cells. FEBS Lett. 2003 Aug 28;550(1-3):57-63. PMID:12935886
↑ Hsu LS, Tsou AP, Chi CW, Lee CH, Chen JY. Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase. J Biomed Sci. 1998;5(2):141-9. PMID:9662074
↑ Cao W, Sohail M, Liu G, Koumbadinga GA, Lobo VG, Xie J. Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation. RNA Biol. 2011 Nov-Dec;8(6):1061-72. doi: 10.4161/rna.8.6.16691. Epub 2011 Nov 1. PMID:21957496 doi:http://dx.doi.org/10.4161/rna.8.6.16691
↑ Kukimoto-Niino M, Yoshikawa S, Takagi T, Ohsawa N, Tomabechi Y, Terada T, Shirouzu M, Suzuki A, Lee S, Yamauchi T, Okada-Iwabu M, Iwabu M, Kadowaki T, Minokoshi Y, Yokoyama S. Crystal structure of the CA2+/calmodulin-dependent protein kinase kinase in complex with the inhibitor STO-609. J Biol Chem. 2011 Apr 19. PMID:21504895 doi:10.1074/jbc.M111.251710

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2zv2"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=609:7-OXO-7H-BENZIMIDAZO[2,1-A]BENZ[DE]ISOQUINOLINE-3-CARBOXYLIC+ACID'>609</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zv2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zv2 RCSB], [http://www.ebi.ac.uk/pdbsum/2zv2 PDBsum], [http://www.topsan.org/Proteins/RSGI/2zv2 TOPSAN]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zv2 OCA], [http://pdbe.org/2zv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zv2 RCSB], [http://www.ebi.ac.uk/pdbsum/2zv2 PDBsum], [http://www.topsan.org/Proteins/RSGI/2zv2 TOPSAN]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
     <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].
+</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=2zv2 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2zv2" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2zv2

From Proteopedia

Revision as of 12:58, 9 February 2016

Crystal structure of human calcium/calmodulin-dependent protein kinase kinase 2, beta, CaMKK2 kinase domain in complex with STO-609

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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