ArticleBMC biology2016
The structure of a prophenoloxidase (PPO) from Anopheles gambiae provides new insights into the mechanism of PPO activation.
Article in BMC biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 46 citations in OpenAlex.
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- Innate Immunity in Insects: The Lights and Shadows of Phenoloxidase System Activation.International journal of molecular sciences · 2025Review
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- Serine protease homolog pairs CLIPA4-A6, A4-A7Δ, and A4-A12 act as cofactors for proteolytic activation of prophenoloxidase-2 and -7 in Anopheles gambiae.Insect biochemistry and molecular biology · 2024Article
- Tyrosinases: a family of copper-containing metalloenzymes.Chemtexts · 2024Article
- An evolutionarily conserved serine protease network mediates melanization and Toll activation inScience advances · 2023Article
- The Crystal Structure of Tyrosinase fromBiomolecules · 2023Article
- Transcriptome Analysis Reveals Early Hemocyte Responses upon In Vivo Stimulation with LPS in the Stick InsectInsects · 2022Article
- Haemocyte-mediated immunity in insects: Cells, processes and associated components in the fight against pathogens and parasites.Immunology · 2021Review
- Similar but Still Different: Which Amino Acid Residues Are Responsible for Varying Activities in Type-III Copper Enzymes?Chembiochem : a European journal of chemical biology · 2021Review
- Laccase Properties, Physiological Functions, and Evolution.International journal of molecular sciences · 2020Review
- Towards Precision Nutrition: A Novel Concept Linking Phytochemicals, Immune Response and Honey Bee Health.Insects · 2019Review
- Extraction optimization, antioxidant activity, and tyrosinase inhibitory capacity of polyphenols fromFood science & nutrition · 2019Article
- Catalytic mechanism of the tyrosinase reaction toward the Tyr98 residue in the caddie protein.PLoS biology · 2018Article
- Activation of Aedes aegypti prophenoloxidase-3 and its role in the immune response against entomopathogenic fungi.Insect molecular biology · 2017Article
- Prophenoloxidase-MediatedFrontiers in immunology · 2017Article
- CLIPB8 is part of the prophenoloxidase activation system in Anopheles gambiae mosquitoes.Insect biochemistry and molecular biology · 2016Article
- Cloning, Expression, and Characterization of Prophenoloxidases from Asian Corn Borer,Journal of immunology research · 2016Article
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4 authors at 1 institution in 1 country.
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Abstract
backgroundPhenoloxidase (PO)-catalyzed melanization is a universal defense mechanism of insects against pathogenic and parasitic infections. In mosquitos such as Anopheles gambiae, melanotic encapsulation is a resistance mechanism against certain parasites that cause malaria and filariasis. PO is initially synthesized by hemocytes and released into hemolymph as inactive prophenoloxidase (PPO), which is activated by a serine protease cascade upon recognition of foreign invaders. The mechanisms of PPO activation and PO catalysis have been elusive.
resultsHerein, we report the crystal structure of PPO8 from A. gambiae at 2.6 Å resolution. PPO8 forms a homodimer with each subunit displaying a classical type III di-copper active center. Our molecular docking and mutagenesis studies revealed a new substrate-binding site with Glu364 as the catalytic residue responsible for the deprotonation of mono- and di-phenolic substrates. Mutation of Glu364 severely impaired both the monophenol hydroxylase and diphenoloxidase activities of AgPPO8. Our data suggested that the newly identified substrate-binding pocket is the actual site for catalysis, and PPO activation could be achieved without withdrawing the conserved phenylalanine residue that was previously deemed as the substrate 'placeholder'.
conclusionsWe present the structural and functional data from a mosquito PPO. Our results revealed a novel substrate-binding site with Glu364 identified as the key catalytic residue for PO enzymatic activities. Our data offered a new model for PPO activation at the molecular level, which differs from the canonical mechanism that demands withdrawing a blocking phenylalanine residue from the previously deemed substrate-binding site. This study provides new insights into the mechanisms of PPO activation and enzymatic catalysis of PO.
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