3gsi

Crystal structure of D552A dimethylglycine oxidase mutant of Arthrobacter globiformis in complex with tetrahydrofolate

spinqualitylabelsall models 3gsi, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gsi is a 1 chain structure with sequence from "achromobacter_globiformis"_(conn_1928)_bergey_et_al._1930 "achromobacter globiformis" (conn 1928) bergey et al. 1930. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, MG, THG Related: 1pj5, 1pj6, 1pj7 Gene: dmg ("Achromobacter globiformis" (Conn 1928) Bergey et al. 1930) Activity: Dimethylglycine oxidase, with EC number 1.5.3.10 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed We report a synthetic biology approach to demonstrate substrate channeling in an unusual bifunctional flavoprotein dimethylglycine oxidase. The catabolism of dimethylglycine through methyl group oxidation can potentially liberate toxic formaldehyde, a problem common to many amine oxidases and dehydrogenases. Using a novel synthetic in vivo reporter system for cellular formaldehyde, we found that the oxidation of dimethylglycine is coupled to the synthesis of 5,10-methylenetetrahydrofolate through an unusual substrate channeling mechanism. We also showed that uncoupling of the active sites could be achieved by mutagenesis or deletion of the 5,10-methylenetetrahydrofolate synthase site and that this leads to accumulation of intracellular formaldehyde. Channeling occurs by nonbiased diffusion of the labile intermediate through a large solvent cavity connecting both active sites. This central "reaction chamber" is created by a modular protein architecture that appears primitive when compared with the sophisticated design of other paradigm substrate-channeling enzymes. The evolutionary origins of the latter were likely similar to dimethylglycine oxidase. This work demonstrates the utility of synthetic biology approaches to the study of enzyme mechanisms in vivo and points to novel channeling mechanisms that protect the cell milieu from potentially toxic reaction products. An internal reaction chamber in dimethylglycine oxidase provides efficient protection from exposure to toxic formaldehyde.,Tralau T, Lafite P, Levy C, Combe JP, Scrutton NS, Leys D J Biol Chem. 2009 Jun 26;284(26):17826-34. Epub 2009 Apr 15. PMID:19369258 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA