1gz3

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[[Image:1gz3.jpg|left|200px]]<br /><applet load="1gz3" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1gz3.jpg|left|200px]]
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caption="1gz3, resolution 2.3&Aring;" />
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'''MOLECULAR MECHANISM FOR THE REGULATION OF HUMAN MITOCHONDRIAL NAD(P)+-DEPENDENT MALIC ENZYME BY ATP AND FUMARATE'''<br />
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{{Structure
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|PDB= 1gz3 |SIZE=350|CAPTION= <scene name='initialview01'>1gz3</scene>, resolution 2.3&Aring;
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|SITE= <scene name='pdbsite=AC1:Fum+Binding+Site+For+Chain+D'>AC1</scene>
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|LIGAND= <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene> and <scene name='pdbligand=FUM:FUMARIC ACID'>FUM</scene>
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|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]
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|GENE=
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}}
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'''MOLECULAR MECHANISM FOR THE REGULATION OF HUMAN MITOCHONDRIAL NAD(P)+-DEPENDENT MALIC ENZYME BY ATP AND FUMARATE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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 <scene name='pdbligand=OXL:'>OXL</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=FUM:'>FUM</scene> 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] Known structural/functional Site: <scene name='pdbsite=AC1:Fum+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZ3 OCA].
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1GZ3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZ3 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12121650 12121650]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12121650 12121650]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]]
[[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]]
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[[Category: allosteric regulation]]
[[Category: allosteric regulation]]
[[Category: energy metabolism]]
[[Category: energy metabolism]]
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[[Category: kinetics]]
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[[Category: kinetic]]
[[Category: mitochondrion.]]
[[Category: mitochondrion.]]
[[Category: nad]]
[[Category: nad]]
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[[Category: protein structure]]
[[Category: protein structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:55:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:29:58 2008''

Revision as of 09:29, 20 March 2008

Image:1gz3.jpg


PDB ID 1gz3

Drag the structure with the mouse to rotate
, resolution 2.3Å
Sites:
Ligands: , , and
Activity: Malate dehydrogenase (oxaloacetate-decarboxylating), with EC number 1.1.1.38
Coordinates: save as pdb, mmCIF, xml



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. 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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