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A novel class of cysteine protease inhibitors: solution structure of staphostatin A from Staphylococcus aureus.
- Source :
-
Biochemistry [Biochemistry] 2003 Nov 25; Vol. 42 (46), pp. 13449-56. - Publication Year :
- 2003
-
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.
- Subjects :
- Amino Acid Substitution
Binding Sites
Carrier Proteins genetics
Carrier Proteins metabolism
Cysteine chemistry
Cysteine Endopeptidases metabolism
Cysteine Proteinase Inhibitors genetics
Cysteine Proteinase Inhibitors metabolism
Models, Molecular
Mutagenesis, Site-Directed
Nuclear Magnetic Resonance, Biomolecular
Oxidation-Reduction
Protein Structure, Secondary
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Solutions chemistry
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Carrier Proteins chemistry
Cysteine Proteinase Inhibitors chemistry
Staphylococcus aureus chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2960
- Volume :
- 42
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 14621990
- Full Text :
- https://doi.org/10.1021/bi035310j