8eyn

Crystal Structure of Human Mitochondrial NADP+ Malic Enzyme 3 in Apo Form

spinqualitylabelsall models 8eyn, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8eyn 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 1.94Å Ligands: CIT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MAON_HUMAN Catalyzes the oxidative decarboxylation of (S)-malate to pyruvate using NADP(+) as a cofactor (PubMed:7818469). Can also reverse the decarboxylation reaction, but only with significantly lower efficiency (PubMed:7818469). Publication Abstract from PubMed Malic enzymes (ME1, ME2, and ME3) are involved in cellular energy regulation, redox homeostasis, and biosynthetic processes, through the production of pyruvate and reducing agent NAD(P)H. Recent studies have implicated the third and least well-characterized isoform, mitochondrial NADP(+)-dependent malic enzyme 3 (ME3), as a therapeutic target for pancreatic cancers. Here, we utilized an integrated structure approach to determine the structures of ME3 in various ligand-binding states at near-atomic resolutions. ME3 is captured in the open form existing as a stable tetramer and its dynamic Domain C is critical for activity. Catalytic assay results reveal that ME3 is a non-allosteric enzyme and does not require modulators for activity while structural analysis suggests that the inner stability of ME3 Domain A relative to ME2 disables allostery in ME3. With structural information available for all three malic enzymes, the foundation has been laid to understand the structural and biochemical differences of these enzymes and could aid in the development of specific malic enzyme small molecule drugs. Integrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer.,Grell TAJ, Mason M, Thompson AA, Gomez-Tamayo JC, Riley D, Wagner MV, Steele R, Ortiz-Meoz RF, Wadia J, Shaffer PL, Tresadern G, Sharma S, Yu X Heliyon. 2022 Dec 19;8(12):e12392. doi: 10.1016/j.heliyon.2022.e12392. , eCollection 2022 Dec. PMID:36590518 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also NADP-dependent malic enzyme

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