1gz3: Difference between revisions
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|PDB= 1gz3 |SIZE=350|CAPTION= <scene name='initialview01'>1gz3</scene>, resolution 2.3Å | |PDB= 1gz3 |SIZE=350|CAPTION= <scene name='initialview01'>1gz3</scene>, resolution 2.3Å | ||
|SITE= <scene name='pdbsite=AC1:Fum+Binding+Site+For+Chain+D'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Fum+Binding+Site+For+Chain+D'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gz3 OCA], [http://www.ebi.ac.uk/pdbsum/1gz3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gz3 RCSB]</span> | |||
}} | }} | ||
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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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Liang, T.]] | [[Category: Liang, T.]] | ||
[[Category: Yang, Z.]] | [[Category: Yang, Z.]] | ||
[[Category: allosteric regulation]] | [[Category: allosteric regulation]] | ||
[[Category: energy metabolism]] | [[Category: energy metabolism]] | ||
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[[Category: protein structure]] | [[Category: protein structure]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:54:18 2008'' | ||
