title: A novel class of cysteine protease inhibitors: solution structure of staphostatin A from Staphylococcus aureus.
abstract: A series of secreted proteases are included among the virulence factors documented for Staphylococcus aureus. In light of increasing antibiotic resistance of this dangerous human pathogen, these proteases are considered as suitable targets for the development of novel therapeutic strategies. The recent discovery of staphostatins, endogenous, highly specific, staphylococcal cysteine protease inhibitors, opened a possibility for structure-based design of low molecular weight analogues. Moreover, the crystal structure of staphostatin B revealed a distinct folding pattern and an unexpected, substrate-like binding mode. The solution structure of staphostatin A reported here confirms that staphostatins constitute a novel, distinct class of cysteine protease inhibitors. In addition, the structure knowledge-based mutagenesis studies shed light on individual structural features of staphostatin A, the inhibition mechanism, and the determinants of distinct specificity of staphostatins toward their target proteases.
authors: Faculty of Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Krakow, Poland. gdubin@mol.uj.edu.pl
authors: Grzegorz
authors: G
authors: Dubin
authors: Marcin
authors: M
authors: Krajewski
authors: Grzegorz
authors: G
authors: Popowicz
authors: Justyna
authors: J
authors: Stec-Niemczyk
authors: Matthias
authors: M
authors: Bochtler
authors: Jan
authors: J
authors: Potempa
authors: Adam
authors: A
authors: Dubin
authors: Tad A
authors: TA
authors: Holak
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013211:Staphylococcus aureus / Q000737:chemistry*
chemical_list: D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D011994:Recombinant Proteins; D012996:Solutions; D003546:Cysteine Endopeptidases; D003545:Cysteine