4cgz: Difference between revisions

Revision as of 02:02, 11 March 2017

Crystal structure of the Bloom's syndrome helicase BLM in complex with DNA

Structural highlights

4cgz is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ADP, ZN
Activity:	DNA helicase, with EC number 3.6.4.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BLM_HUMAN] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[BLM_HUMAN] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Bloom's syndrome helicase (BLM) is a member of the RecQ family of DNA helicases, which play key roles in the maintenance of genome integrity in all organism groups. We describe crystal structures of the BLM helicase domain in complex with DNA and with an antibody fragment, as well as SAXS and domain association studies in solution. We show an unexpected nucleotide-dependent interaction of the core helicase domain with the conserved, poorly characterized HRDC domain. The BLM-DNA complex shows an unusual base-flipping mechanism with unique positioning of the DNA duplex relative to the helicase core domains. Comparison with other crystal structures of RecQ helicases permits the definition of structural transitions underlying ATP-driven helicase action, and the identification of a nucleotide-regulated tunnel that may play a role in interactions with complex DNA substrates.

Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.,Newman JA, Savitsky P, Allerston CK, Bizard AH, Ozer O, Sarlos K, Liu Y, Pardon E, Steyaert J, Hickson ID, Gileadi O Nucleic Acids Res. 2015 Apr 21. pii: gkv373. PMID:25901030^[5]

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

References

↑ Karow JK, Chakraverty RK, Hickson ID. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J Biol Chem. 1997 Dec 5;272(49):30611-4. PMID:9388193
↑ Langland G, Elliott J, Li Y, Creaney J, Dixon K, Groden J. The BLM helicase is necessary for normal DNA double-strand break repair. Cancer Res. 2002 May 15;62(10):2766-70. PMID:12019152
↑ Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011 Feb 15;25(4):350-62. doi: 10.1101/gad.2003811. PMID:21325134 doi:https://dx.doi.org/10.1101/gad.2003811
↑ Wan L, Han J, Liu T, Dong S, Xie F, Chen H, Huang J. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10646-51. doi:, 10.1073/pnas.1220921110. Epub 2013 Mar 18. PMID:23509288 doi:https://dx.doi.org/10.1073/pnas.1220921110
↑ Newman JA, Savitsky P, Allerston CK, Bizard AH, Ozer O, Sarlos K, Liu Y, Pardon E, Steyaert J, Hickson ID, Gileadi O. Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes. Nucleic Acids Res. 2015 Apr 21. pii: gkv373. PMID:25901030 doi:https://dx.doi.org/10.1093/nar/gkv373

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Karow JK, Chakraverty RK, Hickson ID. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J Biol Chem. 1997 Dec 5;272(49):30611-4. PMID:9388193

[2] Langland G, Elliott J, Li Y, Creaney J, Dixon K, Groden J. The BLM helicase is necessary for normal DNA double-strand break repair. Cancer Res. 2002 May 15;62(10):2766-70. PMID:12019152

[3] Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011 Feb 15;25(4):350-62. doi: 10.1101/gad.2003811. PMID:21325134 doi:https://dx.doi.org/10.1101/gad.2003811

[4] Wan L, Han J, Liu T, Dong S, Xie F, Chen H, Huang J. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10646-51. doi:, 10.1073/pnas.1220921110. Epub 2013 Mar 18. PMID:23509288 doi:https://dx.doi.org/10.1073/pnas.1220921110

[5] Newman JA, Savitsky P, Allerston CK, Bizard AH, Ozer O, Sarlos K, Liu Y, Pardon E, Steyaert J, Hickson ID, Gileadi O. Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes. Nucleic Acids Res. 2015 Apr 21. pii: gkv373. PMID:25901030 doi:https://dx.doi.org/10.1093/nar/gkv373

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Bloom's syndrome helicase BLM in complex with DNA==
 <StructureSection load='4cgz' size='340' side='right' caption='[[4cgz]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </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=4cgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cgz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cgz RCSB], [http://www.ebi.ac.uk/pdbsum/4cgz PDBsum]</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=4cgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cgz OCA], [http://pdbe.org/4cgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cgz RCSB], [http://www.ebi.ac.uk/pdbsum/4cgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cgz ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4cgz" style="background-color:#fffaf0;"></div>
 ==See Also==

4cgz: Difference between revisions

Revision as of 02:02, 11 March 2017

Crystal structure of the Bloom's syndrome helicase BLM in complex with DNA

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools