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==Cdc7-Dbf4 bound to ADP-BeF3== | ==Cdc7-Dbf4 bound to ADP-BeF3== | ||
<StructureSection load='6ya8' size='340' side='right'caption='[[6ya8]]' scene=''> | <StructureSection load='6ya8' size='340' side='right'caption='[[6ya8]], [[Resolution|resolution]] 1.79Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YA8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YA8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ya8]] 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=6YA8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YA8 FirstGlance]. <br> | ||
</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=6ya8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ya8 OCA], [http://pdbe.org/6ya8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ya8 RCSB], [http://www.ebi.ac.uk/pdbsum/6ya8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ya8 ProSAT]</span></td></tr> | </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=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='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'>[http://proteopedia.org/fgij/fg.htm?mol=6ya8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ya8 OCA], [http://pdbe.org/6ya8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ya8 RCSB], [http://www.ebi.ac.uk/pdbsum/6ya8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ya8 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ya8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cherepanov P]] | [[Category: Cherepanov, P]] | ||
[[Category: Dick | [[Category: Dick, S D]] | ||
[[Category: Cdc7]] | |||
[[Category: Cell cycle]] | |||
[[Category: Dbf4]] | |||
[[Category: Kinase]] | |||
[[Category: Transferase]] | |||
Revision as of 09:41, 19 August 2020
Cdc7-Dbf4 bound to ADP-BeF3Cdc7-Dbf4 bound to ADP-BeF3
Structural highlights
Function[CDC7_HUMAN] Seems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication. Can phosphorylates MCM2 and MCM3.[1] [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.[2] [3] [4] Publication Abstract from PubMedCDC7 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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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