2cvz
From Proteopedia
(New page: 200px<br /><applet load="2cvz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2cvz, resolution 1.80Å" /> '''Structure of hydroxy...) |
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| - | [[Image:2cvz.gif|left|200px]]<br /><applet load="2cvz" size=" | + | [[Image:2cvz.gif|left|200px]]<br /><applet load="2cvz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2cvz, resolution 1.80Å" /> | caption="2cvz, resolution 1.80Å" /> | ||
'''Structure of hydroxyisobutyrate dehydrogenase from thermus thermophilus HB8'''<br /> | '''Structure of hydroxyisobutyrate dehydrogenase from thermus thermophilus HB8'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 3-Hydroxyisobutyrate, a central metabolite in the valine catabolic | + | 3-Hydroxyisobutyrate, a central metabolite in the valine catabolic pathway, is reversibly oxidized to methylmalonate semialdehyde by a specific dehydrogenase belonging to the 3-hydroxyacid dehydrogenase family. To gain insight into the function of this enzyme at the atomic level, we have determined the first crystal structures of the 3-hydroxyisobutyrate dehydrogenase from Thermus thermophilus HB8: holo enzyme and sulfate ion complex. The crystal structures reveal a unique tetrameric oligomerization and a bound cofactor NADP+. This bacterial enzyme may adopt a novel cofactor-dependence on NADP, whereas NAD is preferred in eukaryotic enzymes. The protomer folds into two distinct domains with open/closed interdomain conformations. The cofactor NADP+ with syn nicotinamide and the sulfate ion are bound to distinct sites located at the interdomain cleft of the protomer through an induced-fit domain closure upon cofactor binding. From the structural comparison with the crystal structure of 6-phosphogluconate dehydrogenase, another member of the 3-hydroxyacid dehydrogenase family, it is suggested that the observed sulfate ion and the substrate 3-hydroxyisobutyrate share the same binding pocket. The observed oligomeric state might be important for the catalytic function through forming the active site involving two adjacent subunits, which seems to be conserved in the 3-hydroxyacid dehydrogenases. A kinetic study confirms that this enzyme has strict substrate specificity for 3-hydroxyisobutyrate and serine, but it cannot distinguish the chirality of the substrates. Lys165 is likely the catalytic residue of the enzyme. |
==About this Structure== | ==About this Structure== | ||
| - | 2CVZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with NDP as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 2CVZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1J3V. Active as [http://en.wikipedia.org/wiki/3-hydroxyisobutyrate_dehydrogenase 3-hydroxyisobutyrate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.31 1.1.1.31] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CVZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
[[Category: Kunishima, N.]] | [[Category: Kunishima, N.]] | ||
| - | [[Category: Lokanath, N | + | [[Category: Lokanath, N K.]] |
[[Category: Miyano, M.]] | [[Category: Miyano, M.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: NDP]] | [[Category: NDP]] | ||
[[Category: hydroxyisobutyrate]] | [[Category: hydroxyisobutyrate]] | ||
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[[Category: valine catabolism]] | [[Category: valine catabolism]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:52:54 2008'' |
Revision as of 14:52, 21 February 2008
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Structure of hydroxyisobutyrate dehydrogenase from thermus thermophilus HB8
Overview
3-Hydroxyisobutyrate, a central metabolite in the valine catabolic pathway, is reversibly oxidized to methylmalonate semialdehyde by a specific dehydrogenase belonging to the 3-hydroxyacid dehydrogenase family. To gain insight into the function of this enzyme at the atomic level, we have determined the first crystal structures of the 3-hydroxyisobutyrate dehydrogenase from Thermus thermophilus HB8: holo enzyme and sulfate ion complex. The crystal structures reveal a unique tetrameric oligomerization and a bound cofactor NADP+. This bacterial enzyme may adopt a novel cofactor-dependence on NADP, whereas NAD is preferred in eukaryotic enzymes. The protomer folds into two distinct domains with open/closed interdomain conformations. The cofactor NADP+ with syn nicotinamide and the sulfate ion are bound to distinct sites located at the interdomain cleft of the protomer through an induced-fit domain closure upon cofactor binding. From the structural comparison with the crystal structure of 6-phosphogluconate dehydrogenase, another member of the 3-hydroxyacid dehydrogenase family, it is suggested that the observed sulfate ion and the substrate 3-hydroxyisobutyrate share the same binding pocket. The observed oligomeric state might be important for the catalytic function through forming the active site involving two adjacent subunits, which seems to be conserved in the 3-hydroxyacid dehydrogenases. A kinetic study confirms that this enzyme has strict substrate specificity for 3-hydroxyisobutyrate and serine, but it cannot distinguish the chirality of the substrates. Lys165 is likely the catalytic residue of the enzyme.
About this Structure
2CVZ is a Single protein structure of sequence from Thermus thermophilus with as ligand. This structure supersedes the now removed PDB entry 1J3V. Active as 3-hydroxyisobutyrate dehydrogenase, with EC number 1.1.1.31 Full crystallographic information is available from OCA.
Reference
Crystal structure of novel NADP-dependent 3-hydroxyisobutyrate dehydrogenase from Thermus thermophilus HB8., Lokanath NK, Ohshima N, Takio K, Shiromizu I, Kuroishi C, Okazaki N, Kuramitsu S, Yokoyama S, Miyano M, Kunishima N, J Mol Biol. 2005 Sep 30;352(4):905-17. PMID:16126223
Page seeded by OCA on Thu Feb 21 16:52:54 2008
Categories: 3-hydroxyisobutyrate dehydrogenase | Single protein | Thermus thermophilus | Kunishima, N. | Lokanath, N K. | Miyano, M. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | NDP | Hydroxyisobutyrate | Nadp+ | Riken structural genomics/proteomics initiative | Rsgi | Structural genomics | Valine catabolism
