1gz3
From Proteopedia
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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 . | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1GZ3 is a | + | 1GZ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with OXL, MN, ATP and FUM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Malate_dehydrogenase_(oxaloacetate-decarboxylating) Malate dehydrogenase (oxaloacetate-decarboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.38 1.1.1.38] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GZ3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein structure]] | [[Category: protein structure]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:53:20 2007'' |
Revision as of 10:48, 5 November 2007
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MOLECULAR MECHANISM FOR THE REGULATION OF HUMAN MITOCHONDRIAL NAD(P)+-DEPENDENT MALIC ENZYME BY ATP AND FUMARATE
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.
About this Structure
1GZ3 is a Single protein structure of sequence from Homo sapiens with OXL, MN, ATP and FUM as ligands. Active as Malate dehydrogenase (oxaloacetate-decarboxylating), with EC number 1.1.1.38 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate., Yang Z, Lanks CW, Tong L, Structure. 2002 Jul;10(7):951-60. PMID:12121650
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