title: Structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase AsaP1.
abstract: The Gram-negative bacterium Aeromonas salmonicida is a fish pathogen for various fish species worldwide. Aeromonas salmonicida subsp. achromogenes produces the extracellular, toxic zinc endopeptidase AsaP1. Crystal structure analyses at 2.0 Å resolution of two proteolytically inactive AsaP1 variants show the polypeptide folding of the protease domain and the propeptide domain. These first crystal structure analyses of a precursor of a deuterolysin-like aspzincin protease provide insights into propeptide function, and specific substrate binding. A lysine side chain of the propeptide binds in the hydrophobic S1'-pocket interacting with three carboxylate side chains. An AsaP1 variant with a lysine to alanine exchange identifies the chaperone function of the propeptide.
authors.affiliation: Department of Molecular Structural Biology, Institute for Biochemistry, University of Greifswald, Germany.|Institute for Biochemistry and Molecular Biology, ZBMZ, Medical Faculty, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Xenia
authors.initials: X
authors.lastname: Bogdanović
authors.affiliation: Department of Molecular Structural Biology, Institute for Biochemistry, University of Greifswald, Germany.
authors.forename: Gottfried J
authors.initials: GJ
authors.lastname: Palm
authors.affiliation: Department of Molecular Structural Biology, Institute for Biochemistry, University of Greifswald, Germany.|Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schwenteit
authors.affiliation: Department of Molecular Structural Biology, Institute for Biochemistry, University of Greifswald, Germany.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, Reykjavík, Iceland.
authors.forename: Bjarnheidur K
authors.initials: BK
authors.lastname: Gudmundsdóttir
authors.affiliation: Department of Molecular Structural Biology, Institute for Biochemistry, University of Greifswald, Germany. winfried.hinrichs@uni-greifswald.de.
authors.forename: Winfried
authors.initials: W
authors.lastname: Hinrichs
mesh_terms: D048409:Aeromonas salmonicida / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding
chemical_list: D001426:Bacterial Proteins; D008666:Metalloendopeptidases; C039830:peptidyl-Lys metalloendopeptidase
keywords: Aeromonas salmonicida subsp. achromogenes; autoprocessing; deuterolysin; intramolecular chaperone; zinc endopeptidase