| Structural highlights
Function
PPAF1_HOLDI Serine endopeptidase which, by cleaving prophenoloxidase PPO1 and PPO2, is required for the activation of the prophenoloxidase cascade probably following the recognition of pathogen-derived products.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A family of serine proteases (SPs) mediates the proteolytic cascades of embryonic development and immune response in invertebrates. These proteases, called easter-type SPs, consist of clip and chymotrypsin-like SP domains. The SP domain of easter-type proteases differs from those of typical SPs in its primary structure. Herein, we report the first crystal structure of the SP domain of easter-type proteases, presented as that of prophenoloxidase activating factor (PPAF)-I in zymogen form. This structure reveals several important structural features including a bound calcium ion, an additional loop with a unique disulfide linkage, a canyon-like deep active site, and an exposed activation loop. We subsequently show the role of the bound calcium and the proteolytic susceptibility of the activation loop, which occurs in a clip domain-independent manner. Based on biochemical study in the presence of heparin, we suggest that PPAF-III, highly homologous to PPAF-I, contains a surface patch that is responsible for enhancing the catalytic activity through interaction with a nonsubstrate region of a target protein. These results provide insights into an activation mechanism of easter-type proteases in proteolytic cascades, in comparison with the well studied blood coagulation enzymes in mammals.
Crystal structure of the serine protease domain of prophenoloxidase activating factor-I.,Piao S, Kim S, Kim JH, Park JW, Lee BL, Ha NC J Biol Chem. 2007 Apr 6;282(14):10783-91. Epub 2007 Feb 7. PMID:17287215[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim MS, Baek MJ, Lee MH, Park JW, Lee SY, Soderhall K, Lee BL. A new easter-type serine protease cleaves a masquerade-like protein during prophenoloxidase activation in Holotrichia diomphalia larvae. J Biol Chem. 2002 Oct 18;277(42):39999-40004. PMID:12185078 doi:10.1074/jbc.M205508200
- ↑ Piao S, Song YL, Kim JH, Park SY, Park JW, Lee BL, Oh BH, Ha NC. Crystal structure of a clip-domain serine protease and functional roles of the clip domains. EMBO J. 2005 Dec 21;24(24):4404-14. Epub 2005 Dec 15. PMID:16362048
- ↑ Piao S, Kim S, Kim JH, Park JW, Lee BL, Ha NC. Crystal structure of the serine protease domain of prophenoloxidase activating factor-I. J Biol Chem. 2007 Apr 6;282(14):10783-91. Epub 2007 Feb 7. PMID:17287215 doi:10.1074/jbc.M611556200
- ↑ Lee SY, Kwon TH, Hyun JH, Choi JS, Kawabata SI, Iwanaga S, Lee BL. In vitro activation of pro-phenol-oxidase by two kinds of pro-phenol-oxidase-activating factors isolated from hemolymph of coleopteran, Holotrichia diomphalia larvae. Eur J Biochem. 1998 May 15;254(1):50-7. PMID:9652393 doi:10.1046/j.1432-1327.1998.2540050.x
- ↑ Lee SY, Cho MY, Hyun JH, Lee KM, Homma KI, Natori S, Kawabata SI, Iwanaga S, Lee BL. Molecular cloning of cDNA for pro-phenol-oxidase-activating factor I, a serine protease is induced by lipopolysaccharide or 1,3-beta-glucan in coleopteran insect, Holotrichia diomphalia larvae. Eur J Biochem. 1998 Nov 1;257(3):615-21. PMID:9839951 doi:10.1046/j.1432-1327.1998.2570615.x
- ↑ Piao S, Kim S, Kim JH, Park JW, Lee BL, Ha NC. Crystal structure of the serine protease domain of prophenoloxidase activating factor-I. J Biol Chem. 2007 Apr 6;282(14):10783-91. Epub 2007 Feb 7. PMID:17287215 doi:10.1074/jbc.M611556200
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