2cvz

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spinqualitylabelsall models 2cvz, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 NDP as ligand. This structure superseeds 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 Sun Nov 25 08:47:32 2007