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| ==Human CDC7 kinase in complex with DBF4 and nucleotide== | | ==Human CDC7 kinase in complex with DBF4 and nucleotide== |
| <StructureSection load='4f99' size='340' side='right' caption='[[4f99]], [[Resolution|resolution]] 2.33Å' scene=''> | | <StructureSection load='4f99' size='340' side='right'caption='[[4f99]], [[Resolution|resolution]] 2.33Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4f99]] 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=4F99 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F99 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4f99]] is a 2 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=4F99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F99 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.33Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f9a|4f9a]], [[4f9b|4f9b]], [[4f9c|4f9c]], [[3pvg|3pvg]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC7, CDC7L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ASK, DBF4, DBF4A, ZDBF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4f99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f99 OCA], [https://pdbe.org/4f99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f99 RCSB], [https://www.ebi.ac.uk/pdbsum/4f99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f99 ProSAT]</span></td></tr> |
| <tr id='activity'><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 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=4f99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f99 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f99 RCSB], [http://www.ebi.ac.uk/pdbsum/4f99 PDBsum]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/DBF4A_HUMAN DBF4A_HUMAN]] Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle.<ref>PMID:10373557</ref> <ref>PMID:10523313</ref> <ref>PMID:17062569</ref> | | [https://www.uniprot.org/uniprot/CDC7_HUMAN CDC7_HUMAN] Seems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication. Can phosphorylates MCM2 and MCM3.<ref>PMID:12065429</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| CDC7 is a serine/threonine kinase that is essential for the initiation of eukaryotic DNA replication. CDC7 activity is controlled by its activator, DBF4. Here we present crystal structures of human CDC7-DBF4 in complex with a nucleotide or ATP-competing small molecules, revealing the active and inhibited forms of the kinase, respectively. DBF4 wraps around CDC7, burying approximately 6,000 A(2) of hydrophobic molecular surface in a bipartite interface. The effector domain of DBF4, containing conserved motif C, is essential and sufficient to support CDC7 kinase activity by binding to the kinase N-terminal lobe and stabilizing its canonical alphaC helix. DBF4 motif M latches onto the C-terminal lobe of the kinase, acting as a tethering domain. Our results elucidate the structural basis for binding to and activation of CDC7 by DBF4 and provide a framework for the design of more potent and specific CDC7 inhibitors.
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| Crystal structure of human CDC7 kinase in complex with its activator DBF4.,Hughes S, Elustondo F, Di Fonzo A, Leroux FG, Wong AC, Snijders AP, Matthews SJ, Cherepanov P Nat Struct Mol Biol. 2012 Nov;19(11):1101-7. doi: 10.1038/nsmb.2404. Epub 2012, Oct 14. PMID:23064647<ref>PMID:23064647</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Non-specific serine/threonine protein kinase]] | | [[Category: Large Structures]] |
| [[Category: Cherepanov, P]] | | [[Category: Cherepanov P]] |
| [[Category: Hughes, S]] | | [[Category: Hughes S]] |
| [[Category: Atp-binding]]
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| [[Category: Cell cycle]]
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| [[Category: Cell division]]
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| [[Category: Dbf4-dependent kinase]]
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| [[Category: Ddk]]
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| [[Category: Mitosis]]
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| [[Category: Nucleotide-binding]]
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| [[Category: Nucleus]]
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| [[Category: Phosphorylation]]
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| [[Category: S phase]]
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| [[Category: Ser/thr protein kinase]]
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| [[Category: Serine/threonine-protein kinase]]
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| [[Category: Transferase]]
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| [[Category: Zinc-binding]]
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