9icd: Difference between revisions

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[[Image:9icd.gif|left|200px]]<br /><applet load="9icd" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:9icd.gif|left|200px]]<br /><applet load="9icd" size="350" color="white" frame="true" align="right" spinBox="true"

caption="9icd, resolution 2.5Å" />

'''CATALYTIC MECHANISM OF NADP+-DEPENDENT ISOCITRATE DEHYDROGENASE: IMPLICATIONS FROM THE STRUCTURES OF MAGNESIUM-ISOCITRATE AND NADP+ COMPLEXES'''<br />

==Overview==

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.

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 Structure==

9ICD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with NAP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=9ICD OCA].

9ICD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=NAP:'>NAP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ICD OCA].

==Reference==

Line 14:

[[Category: Isocitrate dehydrogenase (NADP(+))]]

[[Category: Single protein]]

[[Category: Dean, A.M.]]

[[Category: Dean, A M.]]

[[Category: Hurley, J.H.]]

[[Category: Hurley, J H.]]

[[Category: Koshlandjunior, D.E.]]

[[Category: Koshlandjunior, D E.]]

[[Category: Stroud, R.M.]]

[[Category: Stroud, R M.]]

[[Category: NAP]]

[[Category: oxidoreductase (nad(a)-choh(d))]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Tue Nov 20 13~~:03:~~07 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:18:34 2008''

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@@ Line 1: / Line 1: @@
-[[Image:9icd.gif|left|200px]]<br /><applet load="9icd" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:9icd.gif|left|200px]]<br /><applet load="9icd" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="9icd, resolution 2.5&Aring;" />
 '''CATALYTIC MECHANISM OF NADP+-DEPENDENT ISOCITRATE DEHYDROGENASE: IMPLICATIONS FROM THE STRUCTURES OF MAGNESIUM-ISOCITRATE AND NADP+ COMPLEXES'''<br />
 ==Overview==
-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.
+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 Structure==
-ICD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with NAP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=9ICD OCA].
+ICD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=NAP:'>NAP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ICD OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Isocitrate dehydrogenase (NADP(+))]]
 [[Category: Single protein]]
-[[Category: Dean, A.M.]]
+[[Category: Dean, A M.]]
-[[Category: Hurley, J.H.]]
+[[Category: Hurley, J H.]]
-[[Category: Koshlandjunior, D.E.]]
+[[Category: Koshlandjunior, D E.]]
-[[Category: Stroud, R.M.]]
+[[Category: Stroud, R M.]]
 [[Category: NAP]]
 [[Category: oxidoreductase (nad(a)-choh(d))]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:03:07 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:18:34 2008''