1t0l

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{{STRUCTURE_1t0l| PDB=1t0l | SCENE= }}
{{STRUCTURE_1t0l| PDB=1t0l | SCENE= }}
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'''Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP, isocitrate, and calcium(2+)'''
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===Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP, isocitrate, and calcium(2+)===
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==Overview==
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Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, and regulation of the enzymatic activity of IDHs is crucial for their biological functions. Bacterial IDHs are reversibly regulated by phosphorylation of a strictly conserved serine residue at the active site. Eukaryotic NADP-dependent IDHs (NADP-IDHs) have been shown to have diverse important biological functions; however, their regulatory mechanism remains unclear. Structural studies of human cytosolic NADP-IDH (HcIDH) in complex with NADP and in complex with NADP, isocitrate, and Ca2+ reveal three biologically relevant conformational states of the enzyme that differ substantially in the structure of the active site and in the overall structure. A structural segment at the active site that forms a conserved alpha-helix in all known NADP-IDH structures assumes a loop conformation in the open, inactive form of HcIDH; a partially unraveled alpha-helix in the semi-open, intermediate form; and an alpha-helix in the closed, active form. The side chain of Asp279 of this segment occupies the isocitrate-binding site and forms hydrogen bonds with Ser94 (the equivalent of the phosphorylation site in bacterial IDHs) in the inactive form and chelates the metal ion in the active form. The structural data led us to propose a novel self-regulatory mechanism for HcIDH that mimics the phosphorylation mechanism used by the bacterial homologs, consistent with biochemical and biological data. This mechanism might be applicable to other eukaryotic NADP-IDHs. The results also provide insights into the recognition and specificity of substrate and cofactor by eukaryotic NADP-IDHs.
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{{ABSTRACT_PUBMED_15173171}}
==About this Structure==
==About this Structure==
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[[Category: Quaternary complex]]
[[Category: Quaternary complex]]
[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:21:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 10:53:13 2008''

Revision as of 07:53, 29 July 2008

Image:1t0l.png

Template:STRUCTURE 1t0l

Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP, isocitrate, and calcium(2+)

Template:ABSTRACT PUBMED 15173171

About this Structure

1T0L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity., Xu X, Zhao J, Xu Z, Peng B, Huang Q, Arnold E, Ding J, J Biol Chem. 2004 Aug 6;279(32):33946-57. Epub 2004 Jun 1. PMID:15173171

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