3zo4: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 3zo4 is ON HOLD
+==The Synthesis and Evaluation of Diazaspirocyclic Protein Kinase Inhibitors==
+<StructureSection load='3zo4' size='340' side='right'caption='[[3zo4]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3zo4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZO4 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]] 1.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=QWI:6-(4-PHENYL-1,9-DIAZASPIRO[5.5]UNDECAN-9-YL)-9H-PURINE'>QWI</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=3zo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zo4 OCA], [https://pdbe.org/3zo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zo4 RCSB], [https://www.ebi.ac.uk/pdbsum/3zo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zo4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/IPKA_BOVIN IPKA_BOVIN] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+With the success of protein kinase inhibitors as drugs to target cancer, there is a continued need for new kinase inhibitor scaffolds. We have investigated the synthesis and kinase inhibition of new heteroaryl-substituted diazaspirocyclic compounds that mimic ATP. Versatile syntheses of substituted diazaspirocycles through ring-closing metathesis were demonstrated. Diazaspirocycles directly linked to heteroaromatic hinge binder groups provided ligand efficient inhibitors of multiple kinases, suitable as starting points for further optimization. The binding modes of representative diazaspirocyclic motifs were confirmed by protein crystallography. Selectivity profiles were influenced by the hinge binder group and the interactions of basic nitrogen atoms in the scaffold with acidic side-chains of residues in the ATP pocket. The introduction of more complex substitution to the diazaspirocycles increased potency and varied the selectivity profiles of these initial hits through engagement of the P-loop and changes to the spirocycle conformation, demonstrating the potential of these core scaffolds for future application to kinase inhibitor discovery.
-Authors: Allen, C.E., Chow, C.L., Caldwell, J.J., Westwood, I.M., van Montfort, R.L., Collins, I.
+Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases.,Allen CE, Chow CL, Caldwell JJ, Westwood IM, M van Montfort RL, Collins I Bioorg Med Chem. 2013 Sep 15;21(18):5707-24. doi: 10.1016/j.bmc.2013.07.021. Epub, 2013 Jul 19. PMID:23920481<ref>PMID:23920481</ref>
-Description: The Synthesis and Evaluation of Diazaspirocyclic Protein Kinase Inhibitors
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3zo4" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bos taurus]]
+[[Category: Large Structures]]
+[[Category: Allen CE]]
+[[Category: Caldwell JJ]]
+[[Category: Chow CL]]
+[[Category: Collins I]]
+[[Category: Westwood IM]]
+[[Category: Van Montfort RL]]