Poly (ADP-ribose) polymerase

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== Relevance ==
== Relevance ==
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PARP inhibitors are investigated as mono therapy against breast cancer<ref>PMID:22106552</ref>. Over-expression of PARP-14 rescues myeloma cells from apoptosis.
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PARP inhibitors are investigated as mono therapy against breast cancer<ref>PMID:22106552</ref>. [[Olaparib]] is a PARP inhibitor used as medication against ovarian cancer. Over-expression of PARP-14 rescues myeloma cells from apoptosis.
== Structural highlights ==
== Structural highlights ==
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PARP1 is composed of 3 domains. Among them are the N terminal DNA-binding domain which contains <scene name='43/439963/Cv/3'>3 zinc fingers (residues 1-97, 105-206, 207-366)</scene>. The auto modification (AD) domain which contains a breast cancer 1 protein (BRCT) C-terminus domain (residues 386-485) and a WGR domain (rich in Trp, Gly and Arg) (residues 517-642). The C terminal domain which includes the catalytic domain (or PARP domain) (residues 662-1011)<ref>PMID:19372272</ref>. <scene name='43/439963/Cv/4'>A potential drug binds at the active site pocket</scene><ref>PMID:24922587</ref>.
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PARP1 is composed of 3 domains. Among them are the N terminal DNA-binding domain which contains <scene name='43/439963/Cv/3'>5 zinc fingers (residues 1-97, 105-206, 207-366)</scene>. The auto modification (AD) domain which contains a breast cancer 1 protein (BRCT) C-terminus domain (residues 386-485) and a WGR domain (rich in Trp, Gly and Arg) (residues 517-642). The C terminal domain which includes the catalytic domain (or PARP domain) (residues 662-1011)<ref>PMID:19372272</ref>. <scene name='43/439963/Cv/6'>A potential drug binds at the active site pocket</scene><ref>PMID:24922587</ref>.
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</StructureSection>
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== 3D Structures of Poly (ADP-ribose) polymerase ==
== 3D Structures of Poly (ADP-ribose) polymerase ==
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[[Poly(ADP-ribose) polymerase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Poly (ADP-ribose) polymerase 1; Domains – zinc finger 1 2-96; zinc finger 2 105-206; zinc finger 3 216-366; BRCT 389-487; WGR 517-642; catalytic 662-1101
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**[[3od8]], [[3oda]] – hPARP 1 zinc finger 1 + DNA – human<br />
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**[[2dmj]], [[1v9x]] - hPARP 1 zinc finger 1 - NMR<br />
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**[[3odc]], [[3ode]] - hPARP 1 zinc finger 2 + DNA<br />
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**[[2cs2]], [[2l30]], [[2l31]] - hPARP 1 zinc finger 2 - NMR<br />
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**[[2riq]] - hPARP-1 zinc finger 3<br />
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**[[2jvn]] – hPARP 1 zinc finger 3 – NMR<br />
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**[[4av1]] - hPARP-1 zinc fingers 1,2+ DNA<br />
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**[[2n8a]] - hPARP-1 zinc fingers 1,2+ DNA – NMR<br />
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**[[2cr9]] - hPARP 1 WGR domain – NMR<br />
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**[[3l3l]], [[3l3m]], [[3gn7]], [[4l6s]] – hPARP 1 catalytic domain (mutant) + inhibitor<br />
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**[[2rcw]], [[4pjt]] - hPARP 1 α-helical and catalytic domain + inhibitor<br />
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**[[3gjw]] – hPARP 1 α-helical and catalytic domain (mutant) + inhibitor<br />
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**[[2cok]] – hPARP-1 C terminal (mutant) – NMR<br />
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**[[4dqy]] - hPARP-1 zinc fingers 1,3 and WGR domain + DNA<br />
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**[[2le0]] - PARP-1 BRCT domain – rat - NMR<br />
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**[[3u9h]] – hPARP-1 catalytic domain + nicotinamide<br />
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**[[6bhv]] – hPARP 1 catalytic domain + NAD homolog<br />
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**[[1uk0]], [[1uk1]], [[4gv7]], [[1wok]], [[4hhy]], [[4hhz]], [[2rd6]], [[4r5w]], [[4r6e]], [[4rv6]], [[4und]], [[4uxb]], [[4zzz]], [[5a00]], [[5ds3]], [[5ha9]], [[5xsu]], [[5xst]], [[5xsr]] – hPARP-1 catalytic domain + inhibitor<br />
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**[[3l3l]], [[3l3m]], [[3gn7]], [[4l6s]], [[5kpn]], [[5kpo]], [[5kpp]], [[5kpq]], [[5wrq]], [[5wry]], [[5wrz]], [[5ws0]], [[5ws1]], [[5wtc]] – hPARP 1 catalytic domain (mutant) + inhibitor<br />
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**[[4xhu]] – hPARP 1 catalytic domain + protein homeless homolog<br />
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**[[4opx]], [[4oqa]], [[4oqb]] – hPARP-1 zinc fingers 1,2,3, WGR and catalytic domain + DNA<br />
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*Poly (ADP-ribose) polymerase 2
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**[[3kjd]], [[3kcz]], [[4tvj]], [[4zzx]], [[4zzy]], [[5dsy]] - hPARP 2 catalytic domain + inhibitor<br />
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**[[4pjv]] - hPARP 2 α helical and catalytic domain + inhibitor<br />
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**[[5d5k]] - hPARP 2 residues 1-78 + importin subunit -1 <br />
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**[[1gs0]] - mPARP 2 catalytic domain - mouse
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*Poly (ADP-ribose) polymerase 3
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**[[2eoc]] – hPARP-3 WGR domain – NMR<br />
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**[[3c49]], [[3c4h]], [[3ce0]], [[3fhb]], [[4gv0]], [[4gv2]], [[4gv4]], [[4l6z]], [[4l70]], [[4l7l]], [[4l7n]] [[4l7o]], [[4l7p]], [[4l7r]], [[4l7u]] - hPARP-3 catalytic domain + inhibitor
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*Poly (ADP-ribose) polymerase 9
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**[[5ail]] – hPARP-9 macrodomain 2<br />
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*Poly (ADP-ribose) polymerase 10
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**[[5lx6]] - hPARP 10 catalytic domain + inhibitor<br />
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**[[3hkv]] - hPARP 10 catalytic domain (mutant) + inhibitor<br />
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**[[2dhx]] - hPARP 10 RRM domain
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*Poly (ADP-ribose) polymerase 11
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**[[2dk6]] - hPARP 11 WWE domain – NMR<br />
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*Poly (ADP-ribose) polymerase 12
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**[[2pqf]] - hPARP-12 catalytic domain + inhibitor
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*Poly (ADP-ribose) polymerase 14; Domains – WWE 139-224; macro 1 708-898; macro 2 918-1115; macro 3 1208-1388; catalytic 1611-1801
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**[[3goy]], [[3se2]], [[3smi]], [[3smj]], [[4f1l]], [[4f1q]], [[4py4]], [[5lxp]], [[5lyh]], [[5nqe]], [[5v7t]], [[5v7w]], [[6g0w]] - hPARP 14 catalytic domain + inhibitor<br />
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**[[3q6z]] - hPARP-14 macro domain 1+ ADPR<br />
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**[[3q71]] - hPARP-14 macro domain 2+ ADPR<br />
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**[[5o2d]] - hPARP-14 macro domain 2 (mutant) + inhibitor<br />
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**[[3vfq]], [[4d86]] - hPARP-14 macro domain 1+2 + ADPR<br />
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**[[4abk]] - hPARP-14 macro domain 3+ ADPR<br />
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**[[4abl]] - hPARP-14 macro domain 1<br />
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**[[1x4r]] - mPARP-14 WWE domain – NMR<br />
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*Poly (ADP-ribose) polymerase 15
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**[[3blj]] - hPARP-15 catalytic domain<br />
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**[[4f0e]] - hPARP-15 catalytic domain + ligand<br />
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**[[3gey]] - hPARP-15 catalytic domain + inhibitor<br />
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**[[6ek3]] - hPARP-15 catalytic domain (mutant) + inhibitor<br />
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**[[3v2b]] – hPARP-15 macro domain 2 + ADP<br />
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*Poly (ADP-ribose) polymerase 16
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**[[4f0d]] - hPARP-16 + aminobenzamide
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*Poly (ADP-ribose) polymerase
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**[[1a26]] – cPARP catalytic domain +carba-NAD – chicken<br />
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**[[2paw]] - cPARP catalytic domain<br />
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**[[2pax]], [[4pax]], [[3pax]], [[1pax]], [[1efy]] - cPARP catalytic domain + inhibitor<br />
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**[[5ngo]] – AtPARP Rcd1 PARP domain residues 269-460 – ''Arabidopsis thaliana''<br />
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**[[5n9q]] – AtPARP Rcd1 residues 468-567 <br />
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*Tankyrases 1 (SAM domain 1018-1093; catalytic domain 1093-1325)
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**[[5jti]], [[5ju5]], [[5kni]] - hTank 1 SAM domain<br />
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**[[2rf5]] - hTank 1 catalytic domain (mutant)<br />
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**[[3udd]], [[3uh2]], [[3uh4]], [[4dvi]], [[4i9i]], [[4k4e]], [[4k4f]], [[4krs]], [[4li6]], [[4li7]], [[4li8]], [[4msg]], [[4msk]], [[4mt9]], [[4n3r]], [[4n4v]], [[4oa7]], [[4w5s]], [[4w6e]], [[4tor]], [[4u6a]], [[4uuh]], [[4uw1]], [[5ebt]], [[5ece]] - hTank 1 catalytic domain + inhibitor<br />
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**[[4tos]], [[5ety]] - hTank 1 catalytic domain (mutant) + inhibitor<br />
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**[[5gp7]] - hTank 1 residues 799-957 + USP25<br />
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**[[5jhq]] - hTank 1 residues 174-649 + peptide<br />
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*Tankyrase 2 or PARP 5b (SAM domain 867-940; catalytic domain 946-1113; C-terminal domain 1114-1162)
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**[[5jrt]] - hTank 2 SAM domain<br />
 
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**[[3twq]] - hTank 2 residues 484-655<br />
 
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**[[3twr]], [[3tws]], [[3twt]], [[3twu]], [[3twv]], [[3tww]], [[3twx]], [[4z68]], [[5bxo]], [[5bxu]] - hTank 2 residues 484-655 + peptide substrate<br />
 
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**[[3kr7]] - hTank 2 catalytic domain<br />
 
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**[[4hki]] - hTank 2 catalytic + C terminal domains<br />
 
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**[[3mhk]], [[3mhj]], [[3p0n]], [[3p0p]], [[3p0q]], [[3kr8]], [[3kr8]], [[3u9y]], [[3ua9]], [[3w51]], [[4avu]], [[4avw]], [[4bfp]], [[4bj9]], [[4bjb]], [[4bjc]], [[4bs4]], [[4bu3]], [[4bu5]], [[4bu6]], [[4bu7]], [[4bu8]], [[4bu9]], [[4bua]], [[4bud]], [[4bue]], [[4buf]], [[4bui]], [[4bus]], [[4but]], [[4buu]], [[4buv]], [[4buw]], [[4bux]], [[4buy]], [[4hyf]], [[4iue]], [[4j1z]], [[4j21]], [[4j22]], [[4j3l]], [[4j3m]], [[4m7b]], [[4pml]], [[4pnl]], [[4pnm]], [[4pnn]], [[4pnq]], [[4pnr]], [[4pns]], [[4pnt]], [[4tju]], [[4tjw]], [[4tjy]], [[4tk0]], [[4tk5]], [[4tkf]], [[4tkg]], [[4tki]], [[5aku]], [[5akw]], [[5al1]], [[5al2]], [[5al3]], [[5al4]], [[5al5]], [[4ufu]], [[4uhg]], [[4ui3]], [[4ui4]], [[4ui5]], [[4ui6]], [[4ui7]], [[4ui8]], [[4uvl]], [[4uvn]], [[4uvo]], [[4uvp]], [[4uvs]], [[4uvt]], [[4uvu]], [[4uvv]], [[4uvw]], [[4uvx]], [[4uvy]], [[4uvz]], [[4ux4]], [[4w5i]], [[5adq]], [[5adr]], [[5ads]], [[5adt]], [[5aeh]], [[5owt]], [[5ows]] - hTank 2 catalytic domain+ inhibitor<br />
 
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**[[4hkk]], [[4hkn]], [[4hl5]], [[4hlf]], [[4hlg]], [[4hlh]], [[4hlk]], [[4hlm]], [[4hmh]], [[4kzl]], [[4kzq]], [[4kzu]], [[4l09]], [[4l0b]], [[4l0i]], [[4l0s]], [[4l0t]], [[4l0v]], [[4l10]], [[4l2f]], [[4l2g]], [[4l2k]], [[4l31]], [[4l32]], [[4l33]], [[4l34]], [[5c5p]], [[5c5q]], [[5c5r]], [[5dcz]], [[5fpf]], [[5fpg]], [[5nxe]], [[5nwg]], [[5nwd]], [[5nwc]], [[5nwb]] [[5nvh]], [[5nvf]], [[5nve]], [[5nvc]], [[5nut]], [[5nt4]], [[5nt0]], [[5nsx]], [[5nsp]], [[5nob]], [[4ufy]] - hTank 2 catalytic and C terminal domains + inhibitor<br />
 
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}}
 
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human glycosylated plasminogen complex with acetate, bicarbonate, K+ (purple) and Cl- (green) ions (PDB entry 4hhy)

Drag the structure with the mouse to rotate

References

  1. ↑ Shall S, de Murcia G. Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model? Mutat Res. 2000 Jun 30;460(1):1-15. PMID:10856830
  2. ↑ Dantzer F, Giraud-Panis MJ, Jaco I, Ame JC, Schultz I, Blasco M, Koering CE, Gilson E, Menissier-de Murcia J, de Murcia G, Schreiber V. Functional interaction between poly(ADP-Ribose) polymerase 2 (PARP-2) and TRF2: PARP activity negatively regulates TRF2. Mol Cell Biol. 2004 Feb;24(4):1595-607. PMID:14749375
  3. ↑ Beck C, Robert I, Reina-San-Martin B, Schreiber V, Dantzer F. Poly(ADP-ribose) polymerases in double-strand break repair: focus on PARP1, PARP2 and PARP3. Exp Cell Res. 2014 Nov 15;329(1):18-25. doi: 10.1016/j.yexcr.2014.07.003. Epub, 2014 Jul 10. PMID:25017100 doi:http://dx.doi.org/10.1016/j.yexcr.2014.07.003
  4. ↑ Yu M, Schreek S, Cerni C, Schamberger C, Lesniewicz K, Poreba E, Vervoorts J, Walsemann G, Grotzinger J, Kremmer E, Mehraein Y, Mertsching J, Kraft R, Austen M, Luscher-Firzlaff J, Luscher B. PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene. 2005 Mar 17;24(12):1982-93. PMID:15674325 doi:http://dx.doi.org/1208410
  5. ↑ Karlberg T, Klepsch M, Thorsell AG, Andersson CD, Linusson A, Schuler H. Structural Basis for Lack of ADP-Ribosyltransferase Activity in Poly(ADP-Ribose) Polymerase-13/Zinc Finger Antiviral Protein. J Biol Chem. 2015 Jan 29. pii: jbc.M114.630160. PMID:25635049 doi:http://dx.doi.org/10.1074/jbc.M114.630160
  6. ↑ Barbarulo A, Iansante V, Chaidos A, Naresh K, Rahemtulla A, Franzoso G, Karadimitris A, Haskard DO, Papa S, Bubici C. Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma. Oncogene. 2013 Sep 5;32(36):4231-42. doi: 10.1038/onc.2012.448. Epub 2012 Oct 8. PMID:23045269 doi:http://dx.doi.org/10.1038/onc.2012.448
  7. ↑ Cook BD, Dynek JN, Chang W, Shostak G, Smith S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002 Jan;22(1):332-42. PMID:11739745
  8. ↑ Rios J, Puhalla S. PARP inhibitors in breast cancer: BRCA and beyond. Oncology (Williston Park). 2011 Oct;25(11):1014-25. PMID:22106552
  9. ↑ Altmeyer M, Messner S, Hassa PO, Fey M, Hottiger MO. Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. Nucleic Acids Res. 2009 Jun;37(11):3723-38. doi: 10.1093/nar/gkp229. Epub 2009, Apr 16. PMID:19372272 doi:http://dx.doi.org/10.1093/nar/gkp229
  10. ↑ Patel MR, Bhatt A, Steffen JD, Chergui A, Murai J, Pommier Y, Pascal JM, Trombetta LD, Fronczek FR, Talele TT. Discovery and Structure-Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors. J Med Chem. 2014 Jun 25. PMID:24922587 doi:http://dx.doi.org/10.1021/jm5002502

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