4yzw

Crystal structure of AgPPO8

spinqualitylabelsall models 4yzw, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yzw is a 2 chain structure with sequence from Anopheles gambiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: CU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPO8_ANOGA This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds (Probable). Catalyzes the oxidation of o-diphenols such as dopamine (PubMed:26732497). Also oxidizes monophenols such as tyramine (PubMed:26732497). Publication Abstract from PubMed BACKGROUND: Phenoloxidase (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. RESULTS: Herein, we report the crystal structure of PPO8 from A. gambiae at 2.6 A 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'. CONCLUSIONS: We 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. The structure of a prophenoloxidase (PPO) from Anopheles gambiae provides new insights into the mechanism of PPO activation.,Hu Y, Wang Y, Deng J, Jiang H BMC Biol. 2016 Jan 5;14(1):2. doi: 10.1186/s12915-015-0225-2. PMID:26732497 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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