Sandbox Reserved 1098

This Sandbox is Reserved from 25/11/2019, through 30/9/2020 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1091 through Sandbox Reserved 1115.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

6HMM

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D A enlever quand tout est fini This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue. The 6HMM protein is a humanpoly (ADP-ribose) glycohydrolase. It is an enzyme that will catalyze the hydrolysis of glycosides, here more specifically it will produce a free ADP-ribose. This protein is only present when the DNA is damaged. It influences the damaged chromatin through a derepression on a gene promoter. Consequently this protein is quite interesting for biotechnical applications. Indeed, developing proteins who repair DNA damage is a meaningful goal in research especially in new cancer therapies. Structure Structural highlights This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. Quaternary Structure Poly(ADP-ribose)glycohydrolase interact with PCNA or NUDT5. When this protein is binding with NUDT5 it can remodeling chromatin. Function 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 ligand (of identification number on PDB: 7JB) that can bind to the PARG creating the protein complex 6HMM. Post-translational modifications and anthraquinone There are several possible post-translational modifications to stabilize DNA. Most commonly they would be phosphorylation, acetylation or methylation . 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 . This allows the repair of single-strand breaks on DNA . PARG, a constituent of the 6HMM protein, will degrade PAR to allow the poly (ADP-ribose) polymerase (PARP) to free itself from the damaged, now repaired, site and completes as such reparation . The anthraquinone PDD00013907 is a weakly active and cytotoxic anthraquinone 8a acting as a free ligand binding in the ADP-ribose binding site of the PARG. This PDD00013907 should lead to the inhibition of PARG, which is of interest in the search of novel cancer therapies . The mechanism As said previously, poly(ADP-ribosylation) is an important post-translational modification for DNA repair. The mechanism behind this repair relies on several factors. At first, the Poly (ADP-ribose) polymerase (PARP), more specifically the subtype PARP1, will recognize and will bind to the single-stranded break on the DNA. It will then autophosphorylate due to NAD+ and form PAR chains. These will then recruit other repair proteins to the site. The role of PARG is the hydrolyzation of the specific ribose-ribose bonds present in PAR which leads to its degradation and as such the reparation cycle will be finished. This degradation is important because without PARG the repair cycle cannot be completed and may lead to cell death. This is partially due to the still present PARP on the previously damaged site maintained by the non-degraded PAR .