Download MendeleyCrystal structure of 2-oxoisovalerate and dehydrogenase and the architecture of 2-oxo acid dehydrogenase multienzyme complexes.
Aevarsson, A., Seger, K., Turley, S., Sokatch, J.R., Hol, W.G.(1999) Nat Struct Biol 6: 785-792
- PubMed: 10426958
- DOI: https://doi.org/10.1038/11563
- Primary Citation of Related Structures:
1QS0 - PubMed Abstract:
The family of giant multienzyme complexes metabolizing pyruvate, 2-oxoglutarate, branched-chain 2-oxo acids or acetoin contains several of the largest and most sophisticated protein assemblies known, with molecular masses between 4 and 10 million Da. The principal enzyme components, E1, E2 and E3, are present in numerous copies and utilize multiple cofactors to catalyze a directed sequence of reactions via substrate channeling. The crystal structure of a heterotetrameric (alpha2beta2) E1, 2-oxoisovalerate dehydrogenase from Pseudomonas putida, reveals a tightly packed arrangement of the four subunits with the beta2-dimer held between the jaws of a 'vise' formed by the alpha2-dimer. A long hydrophobic channel, suitable to accommodate the E2 lipoyl-lysine arm, leads to the active site, which contains the cofactor thiamin diphosphate (ThDP) and an inhibitor-derived covalent modification of a histidine side chain. The E1 structure, together with previous structural information on E2 and E3, completes the picture of the shared architectural features of these enormous macromolecular assemblies.
Organizational Affiliation:
Departments of Biological Structure and Biochemistry, Biomolecular Structure Center, University of Washington, P.O. Box 357742, Seattle, Washington 98195-7742, USA.
