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| <StructureSection load='6ya6' size='340' side='right'caption='[[6ya6]], [[Resolution|resolution]] 1.44Å' scene=''> | | <StructureSection load='6ya6' size='340' side='right'caption='[[6ya6]], [[Resolution|resolution]] 1.44Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6ya6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YA6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YA6 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YA6 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0SX:8-CHLORO-2-[(2S)-PYRROLIDIN-2-YL][1]BENZOFURO[3,2-D]PYRIMIDIN-4(3H)-ONE'>0SX</scene>, <scene name='pdbligand=BO3:BORIC+ACID'>BO3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.44Å</td></tr> |
| <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0SX:8-CHLORO-2-[(2S)-PYRROLIDIN-2-YL][1]BENZOFURO[3,2-D]PYRIMIDIN-4(3H)-ONE'>0SX</scene>, <scene name='pdbligand=BO3:BORIC+ACID'>BO3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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 HUMAN]), DBF4, ASK, DBF4A, ZDBF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6ya6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ya6 OCA], [https://pdbe.org/6ya6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ya6 RCSB], [https://www.ebi.ac.uk/pdbsum/6ya6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ya6 ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ya6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ya6 OCA], [http://pdbe.org/6ya6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ya6 RCSB], [http://www.ebi.ac.uk/pdbsum/6ya6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ya6 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[http://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> [[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>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| CDC7 is an essential Ser/Thr kinase that acts upon the replicative helicase throughout the S phase of the cell cycle and is activated by DBF4. Here, we present crystal structures of a highly active human CDC7-DBF4 construct. The structures reveal a zinc-finger domain at the end of the kinase insert 2 that pins the CDC7 activation loop to motif M of DBF4 and the C lobe of CDC7. These interactions lead to ordering of the substrate-binding platform and full opening of the kinase active site. In a co-crystal structure with a mimic of MCM2 Ser40 phosphorylation target, the invariant CDC7 residues Arg373 and Arg380 engage phospho-Ser41 at substrate P+1 position, explaining the selectivity of the S-phase kinase for Ser/Thr residues followed by a pre-phosphorylated or an acidic residue. Our results clarify the role of DBF4 in activation of CDC7 and elucidate the structural basis for recognition of its preferred substrates.
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| Structural Basis for the Activation and Target Site Specificity of CDC7 Kinase.,Dick SD, Federico S, Hughes SM, Pye VE, O'Reilly N, Cherepanov P Structure. 2020 Jun 5. pii: S0969-2126(20)30179-9. doi:, 10.1016/j.str.2020.05.010. PMID:32521228<ref>PMID:32521228</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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| <div class="pdbe-citations 6ya6" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Cherepanov, P]] | | [[Category: Cherepanov P]] |
| [[Category: Dick, S D]] | | [[Category: Dick SD]] |
| [[Category: Bivalent substrate]]
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| [[Category: Cdc7]]
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| [[Category: Cell cycle]]
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| [[Category: Dbf4]]
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| [[Category: Kinase]]
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| [[Category: Transferase]]
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