4f9b: Difference between revisions

Revision as of 16:36, 9 December 2014

Human CDC7 kinase in complex with DBF4 and PHA767491

Structural highlights

4f9b is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	0SY, ZN
Related:	4f99, 4f9a, 4f9c
Gene:	CDC7, CDC7L1 (Homo sapiens), ASK, DBF4, DBF4A, ZDBF1 (Homo sapiens)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hughes S, Elustondo F, Di Fonzo A, Leroux FG, Wong AC, Snijders AP, Matthews SJ, Cherepanov P. Crystal structure of human CDC7 kinase in complex with its activator DBF4. Nat Struct Mol Biol. 2012 Nov;19(11):1101-7. doi: 10.1038/nsmb.2404. Epub 2012, Oct 14. PMID:23064647 doi:https://dx.doi.org/10.1038/nsmb.2404

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OCA

[1] Hughes S, Elustondo F, Di Fonzo A, Leroux FG, Wong AC, Snijders AP, Matthews SJ, Cherepanov P. Crystal structure of human CDC7 kinase in complex with its activator DBF4. Nat Struct Mol Biol. 2012 Nov;19(11):1101-7. doi: 10.1038/nsmb.2404. Epub 2012, Oct 14. PMID:23064647 doi:https://dx.doi.org/10.1038/nsmb.2404

[1]

@@ Line 1: / Line 1: @@
-[[Image:4f9b.png|left|200px]]
+==Human CDC7 kinase in complex with DBF4 and PHA767491==
+<StructureSection load='4f9b' size='340' side='right' caption='[[4f9b]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4f9b]] is a 4 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=4F9B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F9B FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0SY:2-(PYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE'>0SY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f99|4f99]], [[4f9a|4f9a]], [[4f9c|4f9c]]</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='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=4f9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f9b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f9b RCSB], [http://www.ebi.ac.uk/pdbsum/4f9b PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-{{STRUCTURE_4f9b|  PDB=4f9b  |  SCENE=  }}
+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>
-===Human CDC7 kinase in complex with DBF4 and PHA767491===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_23064647}}
+== References ==
+<references/>
-==About this Structure==
+__TOC__
-[[4f9b]] is a 4 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=4F9B OCA].
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Non-specific serine/threonine protein kinase]]
-[[Category: Cherepanov, P.]]
+[[Category: Cherepanov, P]]
-[[Category: Hughes, S.]]
+[[Category: Hughes, S]]
 [[Category: Atp-binding]]
 [[Category: Cell cycle]]

4f9b: Difference between revisions

Revision as of 16:36, 9 December 2014

Human CDC7 kinase in complex with DBF4 and PHA767491

Structural highlights

Publication Abstract from PubMed

References

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