1GZ3

Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate

Summary for 1GZ3

• Entry DOI: 10.2210/pdb1gz3/pdb
• Related: 1DO8 1EFK 1EFL 1GZ4 1QR6
• Descriptor: NAD-dependent malic enzyme, mitochondrial, ADENOSINE-5'-TRIPHOSPHATE, OXALATE ION, ... (6 entities in total)
• Functional Keywords: allosteric regulation, energy metabolism, kinetics, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 251706.50

Authors

Yang, Z.,Lanks, C.W.,Tong, L. (deposition date: 2002-05-14, release date: 2003-05-22, Last modification date: 2024-05-01)

Primary citation

Yang, Z.,Lanks, C.W.,Tong, L.
Molecular Mechanism for the Regulation of Human Mitochondrial Nad(P)+-Dependent Malic Enzyme by ATP and Fumarate
Structure, 10:951-960, 2002

PubMed Abstract: The regulation of human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD-ME) by ATP and fumarate may be crucial for the metabolism of glutamine for energy production in rapidly proliferating tissues and tumors. Here we report the crystal structure at 2.2 A resolution of m-NAD-ME in complex with ATP, Mn2+, tartronate, and fumarate. Our structural, kinetic, and mutagenesis studies reveal unexpectedly that ATP is an active-site inhibitor of the enzyme, despite the presence of an exo binding site. The structure also reveals the allosteric binding site for fumarate in the dimer interface. Mutations in this binding site abolished the activating effects of fumarate. Comparison to the structure in the absence of fumarate indicates a possible molecular mechanism for the allosteric function of this compound.

PubMed: 12121650
DOI: 10.1016/S0969-2126(02)00788-8

Experimental method

X-RAY DIFFRACTION (2.3 Å)