%0 Journal Article %1 ISI:000243366400013 %A Wedde, Marianne %A Weise, Christoph %A Nuck, Rolf %A Altincicek, Boran %A Vilcinskas, Andreas %D 2007 %J BIOLOGICAL CHEMISTRY %K Galleria_mellonella IFZ innate_immunity insects matrix metalloproteinases microbial_metalloproteinases protein_glycosylation %N 1 %P 119-127 %T The insect metalloproteinase inhibitor gene of the lepidopteran Galleria mellonella encodes two distinct inhibitors %V 388 %X The insect metalloproteinase inhibitor (IMPI) from the greater wax moth, Galleria mellonella, represents the first and to date only specific inhibitor of microbial metalloproteinases reported from animals. Here, we report on the characterization including carbohydrate analysis of two recombinant constructs encoded by impi cDNA either upstream or downstream of the furin cleavage site identified. rIMPI-1, corresponding to native IMPI purified from hemolymph, is encoded by the N-terminal part of the impi sequence, whereas rIMPI-2 is encoded by its C-terminal part. rIMPI-1 is glycosylated at N48 with GIcNAc2Man3, showing fucosylation to different extents. Similarly, rIMPI-2 is glycosylated at N149 with GIcNAc2Man3, but is fully fucosylated. rIMPI-1 represents a promising template for the design of second-generation antibiotics owing to its specific activity against thermolysin-like metalloproteinases produced by human pathogenic bacteria such as Vibrio vulnificus. In contrast, rIMPI-2 does not inhibit bacterial metalloproteinases, but is moderately active against recombinant human matrix metalloproteinases (MMPs). Both microbial metalloproteinases and MMPs induce expression of the impi gene when injected into G. mellonella larvae. These findings provide evidence that the impi gene encodes two distinct inhibitors, one inhibiting microbial metalloproteinases and contributing to innate immunity, the other putatively mediating regulation of endogenous MMPs during metamorphosis.

@article{ISI:000243366400013, abstract = {The insect metalloproteinase inhibitor (IMPI) from the greater wax moth, Galleria mellonella, represents the first and to date only specific inhibitor of microbial metalloproteinases reported from animals. Here, we report on the characterization including carbohydrate analysis of two recombinant constructs encoded by impi cDNA either upstream or downstream of the furin cleavage site identified. rIMPI-1, corresponding to native IMPI purified from hemolymph, is encoded by the N-terminal part of the impi sequence, whereas rIMPI-2 is encoded by its C-terminal part. rIMPI-1 is glycosylated at N48 with GIcNAc2Man3, showing fucosylation to different extents. Similarly, rIMPI-2 is glycosylated at N149 with GIcNAc2Man3, but is fully fucosylated. rIMPI-1 represents a promising template for the design of second-generation antibiotics owing to its specific activity against thermolysin-like metalloproteinases produced by human pathogenic bacteria such as Vibrio vulnificus. In contrast, rIMPI-2 does not inhibit bacterial metalloproteinases, but is moderately active against recombinant human matrix metalloproteinases (MMPs). Both microbial metalloproteinases and MMPs induce expression of the impi gene when injected into G. mellonella larvae. These findings provide evidence that the impi gene encodes two distinct inhibitors, one inhibiting microbial metalloproteinases and contributing to innate immunity, the other putatively mediating regulation of endogenous MMPs during metamorphosis.}, added-at = {2008-06-04T15:31:00.000+0200}, author = {Wedde, Marianne and Weise, Christoph and Nuck, Rolf and Altincicek, Boran and Vilcinskas, Andreas}, biburl = {https://www.bibsonomy.org/bibtex/2fddf2ecc186c2a481f183acfc0fdeffd/ifzappliedentomol}, interhash = {68b986571f1749b60a5376ddcf4154f1}, intrahash = {fddf2ecc186c2a481f183acfc0fdeffd}, issn = {1431-6730}, journal = {BIOLOGICAL CHEMISTRY}, keywords = {Galleria_mellonella IFZ innate_immunity insects matrix metalloproteinases microbial_metalloproteinases protein_glycosylation}, number = 1, pages = {119-127}, timestamp = {2008-07-18T14:07:23.000+0200}, title = {The insect metalloproteinase inhibitor gene of the lepidopteran Galleria mellonella encodes two distinct inhibitors}, volume = 388, year = 2007 }