1ika
From Proteopedia
(New page: 200px<br /><applet load="1ika" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ika, resolution 2.7Å" /> '''STRUCTURE OF ISOCITRA...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1ika.gif|left|200px]]<br /><applet load="1ika" size=" | + | [[Image:1ika.gif|left|200px]]<br /><applet load="1ika" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ika, resolution 2.7Å" /> | caption="1ika, resolution 2.7Å" /> | ||
'''STRUCTURE OF ISOCITRATE DEHYDROGENASE WITH ALPHA-KETOGLUTARATE AT 2.7 ANGSTROMS RESOLUTION: CONFORMATIONAL CHANGES INDUCED BY DECARBOXYLATION OF ISOCITRATE'''<br /> | '''STRUCTURE OF ISOCITRATE DEHYDROGENASE WITH ALPHA-KETOGLUTARATE AT 2.7 ANGSTROMS RESOLUTION: CONFORMATIONAL CHANGES INDUCED BY DECARBOXYLATION OF ISOCITRATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of the isocitrate dehydrogenase (IDH) complex with bound | + | The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha-ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha-ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase. |
==About this Structure== | ==About this Structure== | ||
| - | 1IKA 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 CA and AKG as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1IKA 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=CA:'>CA</scene> and <scene name='pdbligand=AKG:'>AKG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1IKA OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Isocitrate dehydrogenase (NADP(+))]] | [[Category: Isocitrate dehydrogenase (NADP(+))]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Junior, D | + | [[Category: Junior, D E.Koshland.]] |
| - | [[Category: Stoddard, B | + | [[Category: Stoddard, B L.]] |
[[Category: AKG]] | [[Category: AKG]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: oxidoreductase(nad(a)-choh(d))]] | [[Category: oxidoreductase(nad(a)-choh(d))]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:12:47 2008'' |
Revision as of 11:12, 21 February 2008
|
STRUCTURE OF ISOCITRATE DEHYDROGENASE WITH ALPHA-KETOGLUTARATE AT 2.7 ANGSTROMS RESOLUTION: CONFORMATIONAL CHANGES INDUCED BY DECARBOXYLATION OF ISOCITRATE
Overview
The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha-ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha-ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase.
About this Structure
1IKA is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Full crystallographic information is available from OCA.
Reference
Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate., Stoddard BL, Koshland DE Jr, Biochemistry. 1993 Sep 14;32(36):9317-22. PMID:8369301
Page seeded by OCA on Thu Feb 21 13:12:47 2008
