1PJ3: Crystal Structure of Human Mitochondrial Nad(p)+-dependent Malic Enzyme in a Pentary Complex With Natural Substrate Pyruvate, Cofactor Nad+, Mn++, and Allosteric Activator Fumarate

Malic enzymes catalyze the oxidative decarboxylation of L-malate to pyruvate and CO(2) with the reduction of the NAD(P)(+) cofactor in the presence of divalent cations. We report the crystal structures at up to 2.1 A resolution of human mitochondrial NAD(P)(+)-dependent malic enzyme in different pentary complexes with the natural substrate malate or pyruvate, the dinucleotide cofactor NAD(+) or NADH, the divalent cation Mn(2+), and the allosteric activator fumarate. Malate is bound deep in the active site, providing two ligands for the cation, and its C4 carboxylate group is out of plane with the C1-C2-C3 atoms, facilitating decarboxylation. The divalent cation is positioned optimally to catalyze the entire reaction. Lys183 is the general base for the oxidation step, extracting the proton from the C2 hydroxyl of malate. Tyr112-Lys183 functions as the general acid-base pair to catalyze the tautomerization of the enolpyruvate product from decarboxylation to pyruvate.
PDB ID: 1PJ3Download
MMDB ID: 25337
PDB Deposition Date: 2003/5/30
Updated in MMDB: 2003/12 
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 1PJ3: tetrameric; determined by author and by software (PISA)
Molecular Components in 1PJ3
Label Count Molecule
Proteins (4 molecules)
Nad-dependent Malic Enzyme, Mitochondrial
Molecule annotation
Chemicals (20 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB