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Structure. 2018 Apr 3;26(4):572-579.e4. doi: 10.1016/j.str.2018.02.008. Epub 2018 Mar 8.

Unique Substrate Specificity of SplE Serine Protease from Staphylococcus aureus.

Author information

1
Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow 30-387, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow 30-387, Poland.
2
Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow 30-387, Poland.
3
Malopolska Centre of Biotechnology, Jagiellonian University, Krakow 30-387, Poland.
4
Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow 30-387, Poland; Department of Biology, College of Science, Salahaddin University, Erbil, 44002 Kurdistan, Iraq.
5
Division of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, 50-370, Poland.
6
Protein Engineering, Novo Nordisk A/S, Maaloev 2880, Denmark.
7
Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.
8
Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow 30-387, Poland; Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA.
9
Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow 30-387, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow 30-387, Poland. Electronic address: grzegorz.dubin@uj.edu.pl.

Abstract

Staphylococcus aureus is a dangerous human pathogen characterized by alarmingly increasing antibiotic resistance. Accumulating evidence suggests the role of Spl proteases in staphylococcal virulence. Spl proteases have restricted, non-overlapping substrate specificity, suggesting that they may constitute a first example of a proteolytic system in bacteria. SplA, SplB, and SplD were previously characterized in terms of substrate specificity and structural determinants thereof. Here we analyze the substrate specificity of SplE documenting its unique P1 preference among Spl proteases and, in fact, among all chymotrypsin-like (family S1) proteases characterized to date. This is interesting since our understanding of the general aspects of proteolysis is based on seminal studies of S1 family members. To better understand the molecular determinants of the unusual specificity of SplE, the crystal structure of the protein is determined here. Conclusions from structural analysis are evaluated by successful grafting of SplE specificity on the scaffold of SplB protease.

KEYWORDS:

SplE; Staphylococcus aureus; proteases; proteinase; structure; substrate specificity

PMID:
29526434
DOI:
10.1016/j.str.2018.02.008
[Indexed for MEDLINE]
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