4Z0Z

Inactive aurone synthase (polyphenol oxidase) from natural source, sulfohistidine ~ 90 %

Summary for 4Z0Z

• Entry DOI: 10.2210/pdb4z0z/pdb
• Descriptor: Aurone synthase, COPPER (II) ION, ... (4 entities in total)
• Functional Keywords: polyphenol oxidase, type iii copper protein, sulfohistidine, inactivation, oxidoreductase
• Biological source: Coreopsis grandiflora (Large-flower tickseed); More
• Total number of polymer chains: 8
• Total formula weight: 167047.71

Authors

Molitor, C.,Mauracher, S.G.,Rompel, A. (deposition date: 2015-03-26, release date: 2016-04-06, Last modification date: 2024-01-10)

Primary citation

Molitor, C.,Mauracher, S.G.,Rompel, A.
Aurone synthase is a catechol oxidase with hydroxylase activity and provides insights into the mechanism of plant polyphenol oxidases.
Proc.Natl.Acad.Sci.USA, 113:E1806-E1815, 2016

PubMed Abstract: Tyrosinases and catechol oxidases belong to the family of polyphenol oxidases (PPOs). Tyrosinases catalyze theo-hydroxylation and oxidation of phenolic compounds, whereas catechol oxidases were so far defined to lack the hydroxylation activity and catalyze solely the oxidation of o-diphenolic compounds. Aurone synthase from Coreopsis grandiflora (AUS1) is a specialized plant PPO involved in the anabolic pathway of aurones. We present, to our knowledge, the first crystal structures of a latent plant PPO, its mature active and inactive form, caused by a sulfation of a copper binding histidine. Analysis of the latent proenzyme's interface between the shielding C-terminal domain and the main core provides insights into its activation mechanisms. As AUS1 did not accept common tyrosinase substrates (tyrosine and tyramine), the enzyme is classified as a catechol oxidase. However, AUS1 showed hydroxylase activity toward its natural substrate (isoliquiritigenin), revealing that the hydroxylase activity is not correlated with the acceptance of common tyrosinase substrates. Therefore, we propose that the hydroxylase reaction is a general functionality of PPOs. Molecular dynamics simulations of docked substrate-enzyme complexes were performed, and a key residue was identified that influences the plant PPO's acceptance or rejection of tyramine. Based on the evidenced hydroxylase activity and the interactions of specific residues with the substrates during the molecular dynamics simulations, a novel catalytic reaction mechanism for plant PPOs is proposed. The presented results strongly suggest that the physiological role of plant catechol oxidases were previously underestimated, as they might hydroxylate their--so far unknown--natural substrates in vivo.

PubMed: 26976571
DOI: 10.1073/pnas.1523575113

Experimental method

X-RAY DIFFRACTION (1.6 Å)