1gz3
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | The regulation of human mitochondrial NAD(P)+-dependent malic enzyme | + | 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== | ==Disease== | ||
| Line 17: | Line 17: | ||
[[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]] | [[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Lanks, C | + | [[Category: Lanks, C W.]] |
[[Category: Liang, T.]] | [[Category: Liang, T.]] | ||
[[Category: Yang, Z.]] | [[Category: Yang, Z.]] | ||
| Line 32: | Line 32: | ||
[[Category: protein structure]] | [[Category: protein structure]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:55:34 2008'' |
Revision as of 10:55, 21 February 2008
|
MOLECULAR MECHANISM FOR THE REGULATION OF HUMAN MITOCHONDRIAL NAD(P)+-DEPENDENT MALIC ENZYME BY ATP AND FUMARATE
Contents |
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.
Disease
Known disease associated with this structure: Epilepsy, idopathic generalized, susceptibility to OMIM:[154270]
About this Structure
1GZ3 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Malate dehydrogenase (oxaloacetate-decarboxylating), with EC number 1.1.1.38 Known structural/functional Site: . 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
Page seeded by OCA on Thu Feb 21 12:55:34 2008
