Malate dehydrogenase (oxaloacetate-decarboxylating)
| malate dehydrogenase (oxaloacetate-decarboxylating) | |||||||||
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ExPASy NiceZyme view | | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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In
enzymology, a malate dehydrogenase (oxaloacetate-decarboxylating) (EC 1.1.1.38) , also termed as malic enzyme 2 (ME2), is an enzyme that catalyzes the chemical reaction
below
- (S)-malate + NAD+ pyruvate + CO2 + NADH
Thus, the two
.This enzyme (ME2) belongs to the family of
pyruvate metabolism
.
Biological function
Malic enzyme 2 participates in pyruvate metabolism and
Krebs cycle intermediate fumarate links metabolism to mitobiogenesis through binding to malic enzyme 2 (ME2). Mechanistically, fumarate binds ME2 with two complementary consequences. First, promoting the formation of ME2 dimers, which activate deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT). DUT fosters thymidine generation and an increase of mtDNA. Second, fumarate-induced ME2 dimers abrogate ME2 monomer binding to mitochondrial ribosome protein L45, freeing it for mitoribosome assembly and mtDNA-encoded protein production. Methylation of the ME2-fumarate binding site by protein arginine methyltransferase-1 inhibits fumarate signaling to constrain mitobiogenesis. Notably, acute myeloid leukemia is highly dependent on mitochondrial function and is sensitive to targeting of the fumarate-ME2 axis.[1]
Structural studies
As of late 2007, 6
structures have been solved for this class of enzymes, with PDB accession codes 1DO8, 1EFK, 1EFL, 1GZ3, 1LLQ, 1O0S, 1PJ2, 1PJ3, 1PJ4, 1PJL, 1QR6, 1WW8, and 2DVM
.
See also
References
- PMID 33770508.
- Kaufman S, Korkes S, Del Campillo A (1951). "Biosynthesis of dicarboxylic acids by carbon dioxide fixation. V Further studies of the "malic" enzyme of Lactobacillus arabinosus". J. Biol. Chem. 192: 301–312. PMID 14917678.
