1t09
From Proteopedia
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| - | [[Image:1t09.gif|left|200px]] | + | [[Image:1t09.gif|left|200px]] |
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| - | '''Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex NADP''' | + | {{Structure |
| + | |PDB= 1t09 |SIZE=350|CAPTION= <scene name='initialview01'>1t09</scene>, resolution 2.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAP:NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'>NAP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] | ||
| + | |GENE= IDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex NADP''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1T09 is a [ | + | 1T09 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=1T09 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15173171 15173171] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Isocitrate dehydrogenase (NADP(+))]] | [[Category: Isocitrate dehydrogenase (NADP(+))]] | ||
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[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:11:56 2008'' |
Revision as of 12:11, 20 March 2008
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| , resolution 2.70Å | |||||||
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| Ligands: | |||||||
| Gene: | IDH (Homo sapiens) | ||||||
| Activity: | Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex NADP
Overview
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.
About this Structure
1T09 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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