View source for 4yzw


==Crystal structure of AgPPO8==
<StructureSection load='4yzw' size='340' side='right'caption='[[4yzw]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yzw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YZW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yzw OCA], [https://pdbe.org/4yzw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yzw RCSB], [https://www.ebi.ac.uk/pdbsum/4yzw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yzw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PPO8_ANOGA 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).<ref>PMID:26732497</ref> <ref>PMID:26732497</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:26732497</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yzw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Anopheles gambiae]]
[[Category: Large Structures]]
[[Category: Hu Y]]