9icd: Difference between revisions

Revision as of 22:53, 4 May 2008

CATALYTIC MECHANISM OF NADP+-DEPENDENT ISOCITRATE DEHYDROGENASE: IMPLICATIONS FROM THE STRUCTURES OF MAGNESIUM-ISOCITRATE AND NADP+ COMPLEXES

OverviewOverview

The structures of NADP+ and magnesium isocitrate bound to the NADP(+)-dependent isocitrate dehydrogenase of Escherichia coli have been determined and refined at 2.5-A resolution. NADP+ is bound by the large domain of isocitrate dehydrogenase, a structure that has little similarity to the supersecondary structure of the nucleotide-binding domain of the lactate dehydrogenase-like family of nucleotide-binding proteins. The coenzyme-binding site confirms the fundamentally different evolution of the isocitrate dehydrogenase-like and the lactate dehydrogenase-like classes of nucleotide-binding proteins. In the magnesium-isocitrate complex, magnesium is coordinated to the alpha-carboxylate and alpha-hydroxyl oxygen of isocitrate in a manner suitable for stabilization of a negative charge on the hydroxyl oxygen during both the dehydrogenation and decarboxylation steps of the conversion of isocitrate to alpha-ketoglutarate. The metal ion is also coordinated by aspartate side chains 283' (of the second subunit of the dimer) and 307 and two water molecules in a roughly octahedral arrangement. On the basis of the geometry of the active site, the base functioning in the dehydrogenation step is most likely aspartate 283'. E. coli isocitrate dehydrogenase transfers a hydride stereospecifically to the A-side of NADP+, and models for a reactive ternary complex consistent with this stereospecificity are discussed.

About this StructureAbout this Structure

9ICD is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes., Hurley JH, Dean AM, Koshland DE Jr, Stroud RM, Biochemistry. 1991 Sep 3;30(35):8671-8. PMID:1888729 Page seeded by OCA on Sun May 4 22:53:16 2008

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OCA

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 [[Image:9icd.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 9icd |SIZE=350|CAPTION= <scene name='initialview01'>9icd</scene>, resolution 2.5&Aring;
+The line below this paragraph, containing "STRUCTURE_9icd", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_9icd|  PDB=9icd  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=9icd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9icd OCA], [http://www.ebi.ac.uk/pdbsum/9icd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=9icd RCSB]</span>
-}}
 '''CATALYTIC MECHANISM OF NADP+-DEPENDENT ISOCITRATE DEHYDROGENASE: IMPLICATIONS FROM THE STRUCTURES OF MAGNESIUM-ISOCITRATE AND NADP+ COMPLEXES'''
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 Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes., Hurley JH, Dean AM, Koshland DE Jr, Stroud RM, Biochemistry. 1991 Sep 3;30(35):8671-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1888729 1888729]
 [[Category: Escherichia coli]]
-[[Category: Isocitrate dehydrogenase (NADP(+))]]
 [[Category: Single protein]]
 [[Category: Dean, A M.]]
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 [[Category: Koshlandjunior, D E.]]
 [[Category: Stroud, R M.]]
-[[Category: oxidoreductase (nad(a)-choh(d))]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 22:53:16 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:46:08 2008''