Sandbox Reserved 1098: Difference between revisions

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In the macro domain fold, a loop is inserted to welcome the Glu115 side chain protecting the active site of the PARG protein. This loop gives PARG the ability to hydrolyze PAR. The  <scene name='82/829351/Parg_active_site/1'>hydrolysis of PAR happens in PARG catalytic domain</scene>. (PAR is represented here in pink).
In the macro domain fold, a loop is inserted to welcome the Glu115 side chain protecting the active site of the PARG protein. This loop gives PARG the ability to hydrolyze PAR. The  <scene name='82/829351/Parg_active_site/1'>hydrolysis of PAR happens in PARG catalytic domain</scene>. (PAR is represented here in pink).


 
=== Post-translational modifications ===


The Poly(ADP-ribose)glycohydrolase can interact with either [[PCNA]] or [[NUDT5]], this gives various possible functions to the protein. When this protein binds with NUDT5 it can remodel chromatin for example [http://www.uniprot.org/uniprot/Q86W56].
The Poly(ADP-ribose)glycohydrolase can interact with either [[PCNA]] or [[NUDT5]], this gives various possible functions to the protein. When this protein binds with NUDT5 it can remodel chromatin for example [http://www.uniprot.org/uniprot/Q86W56].
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The protein is a complex composed of the [[ poly (ADP-ribose) glycohydrolase]] (PARG) and the anthraquinone PDD00013907. The post-translational modifications of the PAR protein (poly ADP-ribose) are important for DNA stability.  
The protein is a complex composed of the [[ poly (ADP-ribose) glycohydrolase]] (PARG) and the anthraquinone PDD00013907. The post-translational modifications of the PAR protein (poly ADP-ribose) are important for DNA stability.  
PDD00013907 is, as already stated, an anthraquinone which is a polycyclic aromatic hydrocarbon usually used in biopesticides as a pest repellant. Here it is considered as a free <scene name='82/829351/7jb/1'>ligand</scene> (of identification number on PDB: 7JB) that can bind to the <scene name='82/829351/Parg/1'>PARG</scene> creating the<scene name='82/829351/Complex/1'> protein complex 6HMM</scene>.  
PDD00013907 is, as already stated, an anthraquinone which is a polycyclic aromatic hydrocarbon usually used in biopesticides as a pest repellant. Here it is considered as a free <scene name='82/829351/7jb/1'>ligand</scene> (of identification number on PDB: 7JB) that can bind to the <scene name='82/829351/Parg/1'>PARG</scene> creating the<scene name='82/829351/Complex/1'> protein complex 6HMM</scene>.  
=== Post-translational modifications and anthraquinone===
 
There are several possible post-translational modifications to stabilize DNA. Most commonly there would be phosphorylation, acetylation or methylation <ref>PMID: 21037856</ref>. Another post-translational modification concerning the 6HMM protein is made on the poly(ADP-ribose) protein (PAR). PAR is composed of a repetition of ADP-ribose units linked through glycosidic ribose-ribose bonds <ref>doi: 10.1038/nature10404</ref>. This allows the repair of single-strand breaks on DNA <ref name="Waszkowycz B, Smith KM, McGonagle AE, Jordan AM, Acton B, Fairweather EE, Griffiths LA, Hamilton NM, Hamilton NS, Hitchin JR, Hutton CP, James DI, Jones CD, Jones S, Mould DP, Small HF, Stowell AIJ, Tucker JA, Waddell ID, Ogilvie DJ. Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides. J Med Chem. 2018 Dec 13;61(23):10767-10792.">DOI: 10.1021/acs.jmedchem.8b01407</ref>. PARG, a constituent of the 6HMM protein, will degrade PAR to allow the poly (ADP-ribose) polymerase (PARP) to free itself from the damaged site, that is now repaired, and completes as such reparation <ref name="James DI, Smith KM, Jordan AM, Fairweather EE, Griffiths LA, Hamilton NS, Hitchin JR, Hutton CP, Jones S, Kelly P, McGonagle AE, Small H, Stowell AI, Tucker J, Waddell ID, Waszkowycz B, Ogilvie DJ. First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG) Inhibit DNA Repair with Differential Pharmacology to Olaparib. ACS Chem Biol. 2016 Oct 12.">PMID: 27689388</ref>.
There are several possible post-translational modifications to stabilize DNA. Most commonly there would be phosphorylation, acetylation or methylation <ref>PMID: 21037856</ref>. Another post-translational modification concerning the 6HMM protein is made on the poly(ADP-ribose) protein (PAR). PAR is composed of a repetition of ADP-ribose units linked through glycosidic ribose-ribose bonds <ref>doi: 10.1038/nature10404</ref>. This allows the repair of single-strand breaks on DNA <ref name="Waszkowycz B, Smith KM, McGonagle AE, Jordan AM, Acton B, Fairweather EE, Griffiths LA, Hamilton NM, Hamilton NS, Hitchin JR, Hutton CP, James DI, Jones CD, Jones S, Mould DP, Small HF, Stowell AIJ, Tucker JA, Waddell ID, Ogilvie DJ. Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides. J Med Chem. 2018 Dec 13;61(23):10767-10792.">DOI: 10.1021/acs.jmedchem.8b01407</ref>. PARG, a constituent of the 6HMM protein, will degrade PAR to allow the poly (ADP-ribose) polymerase (PARP) to free itself from the damaged site, that is now repaired, and completes as such reparation <ref name="James DI, Smith KM, Jordan AM, Fairweather EE, Griffiths LA, Hamilton NS, Hitchin JR, Hutton CP, Jones S, Kelly P, McGonagle AE, Small H, Stowell AI, Tucker J, Waddell ID, Waszkowycz B, Ogilvie DJ. First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG) Inhibit DNA Repair with Differential Pharmacology to Olaparib. ACS Chem Biol. 2016 Oct 12.">PMID: 27689388</ref>.


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