3r22

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<StructureSection load='3r22' size='340' side='right'caption='[[3r22]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
<StructureSection load='3r22' size='340' side='right'caption='[[3r22]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3r22]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R22 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3r22]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R22 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D37:N-{5-[(1-CYCLOHEPTYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-6-YL)AMINO]PYRIDIN-2-YL}METHANESULFONAMIDE'>D37</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3r21|3r21]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D37:N-{5-[(1-CYCLOHEPTYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-6-YL)AMINO]PYRIDIN-2-YL}METHANESULFONAMIDE'>D37</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, ARK1, AURA, BTAK, STK15, STK6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r22 OCA], [https://pdbe.org/3r22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r22 RCSB], [https://www.ebi.ac.uk/pdbsum/3r22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r22 ProSAT]</span></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=3r22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r22 OCA], [https://pdbe.org/3r22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r22 RCSB], [https://www.ebi.ac.uk/pdbsum/3r22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r22 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
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[https://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model.
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Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I).,Zhang L, Fan J, Chong JH, Cesena A, Tam BY, Gilson C, Boykin C, Wang D, Aivazian D, Marcotte D, Xiao G, Le Brazidec JY, Piao J, Lundgren K, Hong K, Vu K, Nguyen K, Gan LS, Silvian L, Ling L, Teng M, Reff M, Takeda N, Timple N, Wang Q, Morena R, Khan S, Zhao S, Li T, Lee WC, Taveras AG, Chao J Bioorg Med Chem Lett. 2011 Jul 13. PMID:21798738<ref>PMID:21798738</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3r22" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Aivazian D]]
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[[Category: Aivazian, D]]
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[[Category: Boykin C]]
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[[Category: Boykin, C]]
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[[Category: Cesana A]]
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[[Category: Brazidec, J Y.Le]]
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[[Category: Chong J-H]]
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[[Category: Cesana, A]]
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[[Category: Fan J]]
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[[Category: Chong, J H]]
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[[Category: Gilson C]]
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[[Category: Fan, J]]
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[[Category: Hong K]]
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[[Category: Gilson, C]]
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[[Category: Le Brazidec J-Y]]
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[[Category: Hong, K]]
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[[Category: Lundgren K]]
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[[Category: Lundgren, K]]
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[[Category: Marcotte D]]
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[[Category: Marcotte, D]]
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[[Category: Nguyen K]]
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[[Category: Nguyen, K]]
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[[Category: Piao J]]
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[[Category: Piao, J]]
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[[Category: Tam B]]
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[[Category: Tam, B]]
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[[Category: Vu K]]
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[[Category: Vu, K]]
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[[Category: Wang D]]
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[[Category: Wang, D]]
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[[Category: Zhang L]]
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[[Category: Zhang, L]]
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[[Category: Kinase domain]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Design, synthesis, and biological evaluation of pyrazolopyridine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I)

PDB ID 3r22

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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