首页|Substrate specificity of Staphylococcus aureus cysteine proteases - Staphopains A, B and C

Substrate specificity of Staphylococcus aureus cysteine proteases - Staphopains A, B and C

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  • Elsevier
Human strains of Staphylococcus aureus secrete two papain-like proteases, staphopain A and B. Avian strains produce another homologous enzyme, staphopain C. Animal studies suggest that staphopains B and C contribute to bacterial virulence, in contrast to staphopain A, which seems to have a virulence unrelated function. Here we present a detailed study of substrate preferences of all three proteases. The specificity of staphopain A, B and C substrate-binding subsites was mapped using different synthetic substrate libraries, inhibitor libraries and a protein substrate combinatorial library. The analysis demonstrated that the most efficiently hydrolyzed sites, using Schechter and Berger nomenclature, comprise a P2-GlyiAla(Ser) sequence motif, where P2 distinguishes the specificity of staphopain A (Leu) from that of both staphopains B and C (Phe/Tyr). However, we show that at the same time the overall specificity of staphopains is relaxed, insofar as multiple substrates that diverge from the sequences described above are also efficiently hydrolyzed.

proteasestaphopainstaphylococcal virulencesubstrates librarysubstrate specificity

Magdalena Kaliriska、Tomasz Kantyka、Doron C. Greenbaum、Katrine S. Larsen、Benedykt Wladyka、Abeer Jabaiah、Matthew Bogyo、Patrick S. Daugherty、Magdalena Wysocka、Marcelina Jaros、Adam Lesner、Krzysztof Rolka、Norbert Schaschke、Henning Stennicke、Adam Dubin、Jan Potempa、Grzegorz Dubin

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Department of Microbiology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Cronostajowa 7, 30-387 Krakow, Poland

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6018, USA

Protein Engineering, Novo Nordisk A/S, 2760 Maaloev, Denmark

Department of Analytical Biochemistry, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Cronostajowa 7, 30-387 Krakow, Poland

Department of Chemical Engineering, University of California at Santa Barbara, Santa Barbara, CA 93106-5080, USA

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA

Faculty of Chemistry, University of Gdansk, Sobieskiego 18/19, 80-952 Gdansk, Poland

Department of Chemistry, Bielefeld University, 33501 Bielefeld, Germany

Department of Microbiology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Cronostajowa 7, 30-387 Krakow, Poland,University of Louisville School of Dentistry, Oral Health and Systemic Disease, Louisville, KY 40202, USA

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2012

10.1016/j.biochi.2011.07.020

Biochimie

Biochimie

SCI
ISSN：0300-9084
年,卷(期)：2012.94(2)
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