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Open data
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Basic information
Entry | Database: PDB / ID: 8.0E+76 | ||||||
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Title | Cryo-EM structure of Apo form ME3 | ||||||
![]() | NADP-dependent malic enzyme, mitochondrial | ||||||
![]() | HYDROLASE / ME1 / ME2 / ME3 / NAD(P)-dependent malic enzymes / Integrated structural techniques / crystal structures / cryo-EM structures / drug discovery / allosteric mechanism | ||||||
Function / homology | ![]() oxygen metabolic process / malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) / malic enzyme activity / malate dehydrogenase (decarboxylating) (NADP+) activity / oxaloacetate decarboxylase activity / malate metabolic process / Pyruvate metabolism / pyruvate metabolic process / NADP+ binding / aerobic respiration ...oxygen metabolic process / malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) / malic enzyme activity / malate dehydrogenase (decarboxylating) (NADP+) activity / oxaloacetate decarboxylase activity / malate metabolic process / Pyruvate metabolism / pyruvate metabolic process / NADP+ binding / aerobic respiration / NAD binding / mitochondrial matrix / mitochondrion / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.51 Å | ||||||
![]() | Yu, X. / Grell, T.A.J. / Shaffer, P.L. / Steele, R. / Sharma, S. / Thompson, A.A. / Tresadern, G. / Ortiz-Meoz, R.F. / Mason, M. / Gomez-Tamayo, J.C. ...Yu, X. / Grell, T.A.J. / Shaffer, P.L. / Steele, R. / Sharma, S. / Thompson, A.A. / Tresadern, G. / Ortiz-Meoz, R.F. / Mason, M. / Gomez-Tamayo, J.C. / Riley, D. / Wagner, M.V. / Wadia, J. | ||||||
Funding support | 1items
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![]() | ![]() Title: Integrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer. Authors: Tsehai A J Grell / Mark Mason / Aaron A Thompson / Jose Carlos Gómez-Tamayo / Daniel Riley / Michelle V Wagner / Ruth Steele / Rodrigo F Ortiz-Meoz / Jay Wadia / Paul L Shaffer / Gary ...Authors: Tsehai A J Grell / Mark Mason / Aaron A Thompson / Jose Carlos Gómez-Tamayo / Daniel Riley / Michelle V Wagner / Ruth Steele / Rodrigo F Ortiz-Meoz / Jay Wadia / Paul L Shaffer / Gary Tresadern / Sujata Sharma / Xiaodi Yu / ![]() ![]() 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 ...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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 351.7 KB | Display | ![]() |
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PDB format | ![]() | 287 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27936MC ![]() 8e78C ![]() 8e8oC ![]() 8eynC ![]() 8eyoC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 67151.250 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q16798, malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Cryo-EM structure of Apo ME3 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.51 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 473519 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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