Structures of human Malic Enzyme 3
Grell, T. A. J.; Mason, M.; Thompson, A. A.; Gomez-Tamayo, J. C.; Riley, D.; Wagner, M. V.; Steele, R.; Ortiz-Meoz, R. F.; Wadia, J.; Shaffer, P. L.; Tresadern, G.; Sharma, S.; Yu, X.
Show abstract
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 capture the structures of ME3 in various ligand binding states. ME3 exists 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.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structural Basis of Protein Arginine Methyltransferase Activation by a Catalytically Dead Homolog (Prozyme) 95%
- The crystal structure of the Ca2+-ATPase 1 from Listeria monocytogenes reveals a pump primed for dephosphorylation 94%
- A F420-dependent single domain chemogenetic tool for protein de-dimerization 94%
Similar papers in this journal
- Structural basis of S-adenosylmethionine-dependent Allosteric Transition from Active to Inactive States in Methylenetetrahydrofolate Reductase 93%
- Cryo-EM structure of Helicobacter pylori urease with a novel inhibitor in the active site at 2.0 A resolution 93%
- The molecular basis of Human FN3K mediated phosphorylation of glycated substrate 92%
Similar papers in this journal
- Mechanistic implications of the ternary complex structural models for the photoenzyme protochlorophyllide oxidoreductase. 93%
- Paradigms of convergent evolution in enzymes 93%
- Solubility, Hydration, and Sulphate Coordination in Cubic Insulin Crystals from Esrapid™ Monomers Stabilized in Divalent Anionic Form of Citric Acid 93%
Similar papers in this journal
- Oxygen-induced chromophore degradation in the photoswitchable red fluorescent protein rsCherry 93%
- Structural studies of KCTD1 and its disease-causing mutant P20S provide insights into the protein function and misfunction 92%
- Structural framework for the understanding spectroscopic and functional signatures of the cyanobacterial Orange Carotenoid Protein families 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.