6x1y

Mre11 dimer in complex with small molecule modulator PFMI

spinqualitylabelsall models 6x1y, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6x1y is a 2 chain structure with sequence from Thermotoga maritima. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: MES, UKV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9X1X0_THEMA Publication Abstract from PubMed Cancer will directly affect the lives of over one-third of the population. The DNA Damage Response (DDR) is an intricate system involving damage recognition, cell cycle regulation, DNA repair, and ultimately cell fate determination, playing a central role in cancer etiology and therapy. Two primary therapeutic approaches involving DDR targeting include: combinatorial treatments employing anticancer genotoxic agents; and synthetic lethality, exploiting a sporadic DDR defect as a mechanism for cancer-specific therapy. Whereas, many DDR proteins have proven "undruggable", Fragment- and Structure-Based Drug Discovery (FBDD, SBDD) have advanced therapeutic agent identification and development. FBDD has led to 4 (with approximately 50 more drugs under preclinical and clinical development), while SBDD is estimated to have contributed to the development of >200, FDA-approved medicines. Protein X-ray crystallography-based fragment library screening, especially for elusive or "undruggable" targets, allows for simultaneous generation of hits plus details of protein-ligand interactions and binding sites (orthosteric or allosteric) that inform chemical tractability, downstream biology, and intellectual property. Using a novel high-throughput crystallography-based fragment library screening platform, we screened five diverse proteins, yielding hit rates of approximately 2-8% and crystal structures from approximately 1.8 to 3.2 A. We consider current FBDD/SBDD methods and some exemplary results of efforts to design inhibitors against the DDR nucleases meiotic recombination 11 (MRE11, a.k.a., MRE11A), apurinic/apyrimidinic endonuclease 1 (APE1, a.k.a., APEX1), and flap endonuclease 1 (FEN1). Fragment- and structure-based drug discovery for developing therapeutic agents targeting the DNA Damage Response.,Wilson DM 3rd, Deacon AM, Duncton MAJ, Pellicena P, Georgiadis MM, Yeh AP, Arvai AS, Moiani D, Tainer JA, Das D Prog Biophys Mol Biol. 2020 Oct 25. pii: S0079-6107(20)30111-5. doi:, 10.1016/j.pbiomolbio.2020.10.005. PMID:33115610 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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