9s17: Difference between revisions

Latest revision as of 05:00, 27 May 2026

WRN helicase in complex with molecule 81

Structural highlights

9s17 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.91Å
Ligands:	A1JKV, DMS, EDO, PEG, SO4, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

WRN_HUMAN Defects in WRN are a cause of Werner syndrome (WRN) [MIM:277700. WRN is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction. Currently all known WS mutations produces prematurely terminated proteins.^[1] Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:114500.

Function

WRN_HUMAN Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity).^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67. PMID:16673358 doi:10.1002/humu.20337
↑ Xue Y, Ratcliff GC, Wang H, Davis-Searles PR, Gray MD, Erie DA, Redinbo MR. A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities. Biochemistry. 2002 Mar 5;41(9):2901-12. PMID:11863428
↑ Kamath-Loeb AS, Lan L, Nakajima S, Yasui A, Loeb LA. Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10394-9. Epub 2007 Jun 11. PMID:17563354 doi:10.1073/pnas.0702513104
↑ Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD. The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J Biol Chem. 2008 Sep 5;283(36):24478-83. doi: 10.1074/jbc.M803370200. Epub 2008 , Jul 2. PMID:18596042 doi:10.1074/jbc.M803370200
↑ Zecevic A, Menard H, Gurel V, Hagan E, DeCaro R, Zhitkovich A. WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle. 2009 Sep 1;8(17):2769-78. Epub 2009 Sep 2. PMID:19652551
↑ Opresko PL, Sowd G, Wang H. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One. 2009;4(3):e4825. doi: 10.1371/journal.pone.0004825. Epub 2009 Mar 13. PMID:19283071 doi:10.1371/journal.pone.0004825

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OCA

[1] Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67. PMID:16673358 doi:10.1002/humu.20337

[2] Xue Y, Ratcliff GC, Wang H, Davis-Searles PR, Gray MD, Erie DA, Redinbo MR. A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities. Biochemistry. 2002 Mar 5;41(9):2901-12. PMID:11863428

[3] Kamath-Loeb AS, Lan L, Nakajima S, Yasui A, Loeb LA. Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10394-9. Epub 2007 Jun 11. PMID:17563354 doi:10.1073/pnas.0702513104

[4] Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD. The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J Biol Chem. 2008 Sep 5;283(36):24478-83. doi: 10.1074/jbc.M803370200. Epub 2008 , Jul 2. PMID:18596042 doi:10.1074/jbc.M803370200

[5] Zecevic A, Menard H, Gurel V, Hagan E, DeCaro R, Zhitkovich A. WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle. 2009 Sep 1;8(17):2769-78. Epub 2009 Sep 2. PMID:19652551

[6] Opresko PL, Sowd G, Wang H. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One. 2009;4(3):e4825. doi: 10.1371/journal.pone.0004825. Epub 2009 Mar 13. PMID:19283071 doi:10.1371/journal.pone.0004825

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9s17 is ON HOLD  until Paper Publication
+==WRN helicase in complex with molecule 81==
+<StructureSection load='9s17' size='340' side='right'caption='[[9s17]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9s17]] 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=9S17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9S17 FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JKV:(2~{R},4~{R})-4-ethyl-~{N}-[(2~{S})-4-methylsulfonylbutan-2-yl]-2-phenyl-piperidine-1-carboxamide'>A1JKV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=9s17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9s17 OCA], [https://pdbe.org/9s17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9s17 RCSB], [https://www.ebi.ac.uk/pdbsum/9s17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9s17 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/WRN_HUMAN WRN_HUMAN] Defects in WRN are a cause of Werner syndrome (WRN) [MIM:[https://omim.org/entry/277700 277700]. WRN is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction. Currently all known WS mutations produces prematurely terminated proteins.<ref>PMID:16673358</ref>   Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].
+== Function ==
+[https://www.uniprot.org/uniprot/WRN_HUMAN WRN_HUMAN] Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity).<ref>PMID:11863428</ref> <ref>PMID:17563354</ref> <ref>PMID:18596042</ref> <ref>PMID:19652551</ref> <ref>PMID:19283071</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Fletcher CT]]
+[[Category: Rucktooa P]]

9s17: Difference between revisions

Latest revision as of 05:00, 27 May 2026

WRN helicase in complex with molecule 81

Structural highlights

Disease

Function

References

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