1gz3: Difference between revisions
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==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known disease associated with this structure: Epilepsy, idopathic generalized, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154270 154270]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: protein structure]] | [[Category: protein structure]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:10:17 2007'' | ||
