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==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==

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[[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]]

[[Category: Single protein]]

[[Category: Lanks, C.W.]]

[[Category: Lanks, C W.]]

[[Category: Liang, T.]]

[[Category: Yang, Z.]]

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[[Category: protein structure]]

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@@ Line 4: / Line 4: @@
 ==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==
@@ Line 17: / Line 17: @@
 [[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]]
 [[Category: Single protein]]
-[[Category: Lanks, C.W.]]
+[[Category: Lanks, C W.]]
 [[Category: Liang, T.]]
 [[Category: Yang, Z.]]
@@ Line 32: / Line 32: @@
 [[Category: protein structure]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:44:11 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:55:34 2008''