2NP9

Crystal structure of a dioxygenase in the Crotonase superfamily

Summary for 2NP9

• Entry DOI: 10.2210/pdb2np9/pdb
• Descriptor: DpgC, [(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL (3R)-4-({3-[(2-{[(3,5-DIHYDROXYPHENYL)ACETYL]AMINO}ETHYL)AMINO]-3-OXOPROPYL}AMINO)-3-HYDROXY-2,2-DIMETHYL-4-OXOBUTYL DIHYDROGEN DIPHOSPHATE, OXYGEN MOLECULE, ... (4 entities in total)
• Functional Keywords: protein inhibitor complex, oxidoreductase
• Biological source: Streptomyces toyocaensis
• Total number of polymer chains: 3
• Total formula weight: 147905.63

Authors

Bruner, S.D.,Widboom, P.F.,Fielding, E.N. (deposition date: 2006-10-26, release date: 2007-05-22, Last modification date: 2024-04-03)

Primary citation

Widboom, P.F.,Fielding, E.N.,Liu, Y.,Bruner, S.D.
Structural basis for cofactor-independent dioxygenation in vancomycin biosynthesis.
Nature, 447:342-345, 2007

PubMed Abstract: Enzyme-catalysed oxidations are some of the most common transformations in primary and secondary metabolism. The vancomycin biosynthetic enzyme DpgC belongs to a small class of oxygenation enzymes that are not dependent on an accessory cofactor or metal ion. The detailed mechanism of cofactor-independent oxygenases has not been established. Here we report the first structure of an enzyme of this oxygenase class in complex with a bound substrate mimic. The use of a designed, synthetic substrate analogue allows unique insights into the chemistry of oxygen activation. The structure confirms the absence of cofactors, and electron density consistent with molecular oxygen is present adjacent to the site of oxidation on the substrate. Molecular oxygen is bound in a small hydrophobic pocket and the substrate provides the reducing power to activate oxygen for downstream chemical steps. Our results resolve the unique and complex chemistry of DpgC, a key enzyme in the biosynthetic pathway of an important class of antibiotics. Furthermore, mechanistic parallels exist between DpgC and cofactor-dependent flavoenzymes, providing information regarding the general mechanism of enzymatic oxygen activation.

PubMed: 17507985
DOI: 10.1038/nature05702

Experimental method

X-RAY DIFFRACTION (2.45 Å)