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Amino Acid Residues Modulating the Activities of Staphylococcal Glutamyl Title Endopeptidases

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Amino Acid Residues Modulating the Activities of Staphylococcal Glutamyl Title Endopeptidases NAOSITE: Nagasaki University's Academic Output SITE Amino acid residues modulating the activities of staphylococcal glutamyl Title endopeptidases. Ono, Toshio; Ohara-Nemoto, Yuko; Shimoyama, Yu; Okawara, Hisami; Author(s) Kobayakawa, Takeshi; Baba, Tomomi T; Kimura, Shigenobu; Nemoto, Takayuki K Citation Biological chemistry, 391(10), pp.1221-1232; 2010 Issue Date 2010-10 URL http://hdl.handle.net/10069/24535 Right © 2010 by Walter de Gruyter Berlin New York 2010. This document is downloaded at: 2020-09-18T02:19:01Z http://naosite.lb.nagasaki-u.ac.jp BIOLOGICAL CHEMISTRY Founded in 1877 by Felix Hoppe-Seyler as EDITOR-IN-CHIEF Zeitschriftfur PhysioLogische Chemie H. Sies, DUsseldorf Felix Hoppe-Seyler (1825-1895) was a pioneer of biochemistry, EXECUTIVE EDITORS remembered not only for hi s di scovery of hemoglobin and F. U. Hart!, Martinsried hi s contributions to the chemical characterization of many other S. LudlVig, MUnster biological compounds and processes but also for having been the K. Sandhoff, Bonn mentor of Friedrich Miescher and Albrecht Kossel. In hi s preface B. Turk, Ljubljana to the first issue of Zeitschrift fur Physiologische Chemie, A. Wittinghofer, Dortmund Feli x Hoppe-Seyler coined the term Biochemistry (,Biochemie' ) for the then newly emerging di scipline. ASSOCIATE EDITORS (GBM STUDY GROUPS) C.-M. Becker, Erlangen F. Bier, Nuthetal G. BoL, Berlin R. Brandt, OsnabrUck R. Frank, Braunschweig T. Friedrich, Freiburg K. Giehl, Giessen F.-G. Hanisch, Cologne D. Heinz, Braunschweig D. KLostermeier, Basel I. Koch, Frankfurt/Main T. Roitsch, WUrzburg C. SeideL, DUsseldorf R. Tampe, Frankfurt/Main D. WoLf, Stuttgart EDITORIAL BOARD W Baumeister, Martinsried B. Brune, Frankfurt/Main B. Bukau, Heidelberg H. Fritz, Munich C. Hammann, Darmstadt D. Haussingel; DUsseldorf R . Kornberg, Stanford A. Kruger, Munich V. MagdoLen, Munich M. Muschen, Los Angeles G. PejLer, Uppsala N. Pfanner, Freiburg R. Pike, Melbourne J. Potempa, Krakow M. Ryan, Melbourne P. Saftig, Kiel W Schaffnel; ZUrich Biological Chemi stry is associated C. Sommerhoff, Munich with the Gesell schaft fUr Biochemie und D. WilLbold, DUsseldorf Moleku larbiologie e.V (GBM) DE GRUYTER BioI. Chern., Vol. 391, pp. 1221-1232, October 2010· Copyright © by Walter de Gruyter· Berlin· New York. DOI10.1515/BC .2010.116 Amino acid residues modulating the activities of staphylococcal glutamyl endopeptidases 2 Toshio Ono\ Yuko Ohara-Nemoto\ Yu Shimoyama , important virulence factors. One of these abundantly secreted Hisami Okawara\ Takeshi KobayakawaI, extracellular proteases is a serine protease, GluV8, also l 2 Tomomi T. Baba , Shigenobu Kimura and known as V8 protease/SspNGlu-C (Drapeau et aI. , 1972; 1 Takayuki K. Nemoto ,:;, Rice et aI., 2001). GluV8 contributes to the growth and sur­ vival of this microorganism in animal models (Coulter et aI., I Department of Oral Molecular Biology, Course of 1998) and plays a key role in degrading fibronectin-binding Medical and Dental Sciences, Nagasaki University proteins and protein A, which are adhesion molecules on the Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, staphylococcal surface (Karlsson et aI. , 2001). S. aureus Nagasaki 852-8588, Japan infection triggers the production of inhibitory antibodies 2 Department of Pathogenesis and Control of Oral Diseases, against GluV8 in mice, suggesting that the immunological Division of Oral Microbiology and Immunology, Iwate response to GluV8 could be an important host-defense mech­ Medical University School of Dentistry, 1-3-27 Chuodori, anism (Calander et aI., 2008). Morioka 020-8505, Japan GluV8 belongs to the glutamyl endopeptidase I family 8 Corresponding author (EC 3.4.21.19), whereby members specifically cleave the e-mail: [email protected] carboxyl side of the peptide bond of negatively charged resi­ dues, i.e., glutamic acid and, much less potently, aspartic acid Abstract (S tennicke and Breddam, 1998). In staphylococci, GluV8 family members are expressed in S. aureus (Drapeau et aI. , The glutamyl endopeptidase family of enzymes from staph­ 1972), Staphylococcus epidermidis (designated GluSE; Sasa­ ylococci has been shown to be important virulence deter­ ki et aI. , 1998; Dubin et aI. , 2001; Ohara-Nemoto et aI., minants of pathogenic family members, such as 2002), and Staphylococcus wa rneri (GluSW; Yokoi et aI. , Staphylococcus aureus. Previous studies have identified the 2001). Members of the GluV8 family are also expressed in N-terminus and residues from positions 185- 195 as poten­ Bacillus licheniformis (Kakudo et aI., 1992; Svendsen and tially important regions that determine the activity of three Breddam, 1992), Bacillus intermedius (Rebrikov et aI., 1999; members of the family. Cloning and sequencing of the new Demidyuk et aI. , 2004), Enterococcus faecalis (Kawalec et family members from Staphylococcus caprae (GluScpr) and aI., 2005), Streptomyces fradiae (Kitadokoro et aI., 1993), Staphylococcus cohnii (GluScoh) revealed that the N-termi­ and Streptomyces griseus (Svendsen et aI. , 1991 ; Suzuki et nal Val residue is maintained in all family members. Mutants aI. , 1994), suggesting important roles of these proteases in of the GluV8 enzyme from S. aureus with altered N-terminal the life of these bacteria. Therefore, it is reasonable to pos­ residues, including amino acids with similar properties, were tulate that other staphylococcal species also produce these inactive, indicating that the Val residue is specifically endopeptidases. In fact, the genome project of Staphylococ­ required at the N-terminus of this enzyme family in order cus saprophyticus revealed the existence of the gene encod­ for them to function correctly. Recombinant GluScpr was ing a GluV8 family endopeptidase (Figure 1), although the found to have peptidase activity intermediate between GluV8 protein expression of it has not been achieved yet (Kuroda and GluSE from Staphylococcus epidermis and to be some­ et aI., 2005). what less specific in its substrate requirements than other Drapeau (1978) found that maturation of GluV8 zymogen family members. The 185-195 region was found to contrib­ is mediated by a thermolysin family enzyme, aureolysin, that ute to the activity of GluScpr, although other regions of the exhibits a preference for hydrophobic amino acids in the PI' enzyme must also playa role in defining the activity. Our position of its substrates. In accordance with this finding, results strongly indicate the importance of the N-terminal and recombinant GluV8 expressed in Escherichia coli can be the 185-195 region in the activity of the glutamyl endopep­ efficiently processed into the mature form by thermolysin tidases of staphylococci. treatment in vitro (Nemoto et aI., 2008). Because V is com­ Keywords: processing; Staphylococcus aureus; monly located at the N-termini of all mature enzymes studied Staphylococcus cap rae; Staphylococcus cohnii; thus far (Ono et aI. , 2008; Figure 1), the thermolysin family Staphylococcus epidermidis; thermolysin. enzymes could be responsible for processing of all staphy­ lococcal glutamyl endopeptidases. In addition to a ro le of the pro-mature border, the protonated a -amino group of VI was Introduction reported to be important for the recognition of a substrate peptide (Prasad et aI. , 2004). However, if these two are the Staphylococcus aureus, a frequent pathogen in human dis­ entire roles of VI, any hydrophobic amino acids (L, Y, I, ease, produces extracellular proteases, which are regarded as and F) and A can be located at the N-terminus of mature 1222 T. Ono et al. A -68 -60 pre -50 -40 -30 pro -20 -10 -1 I. I ~ ' ~ I I . ' S . aureus MKGKFLKIfSSLFVATLTTJI.TLVSSPAANALSSKAHD.-HPQQTQSSKQQTPKIQ-KGG LKPLEQREHAN S . epidermidis !'1KKRFLSICTNTlAALATTTMVN--TSYAKTDTESHNHSSLGTENKNVLDINS-SSHNIKPSQ_ KSYPS S . warner i MKVKFFTASSLLIATLTS.lI.TLIN-- PAIiAETTSSTDNHQQTTQSQQQKTPKI D-KGNNVKPVEKKERAN S . saprop.IJyticus !'ILKRKLRGGLIFIIALLCTVISINGNTYAATQTHQSTDQSAQSEDJI.KVG-------------TNQIKTR S . caprae MRKFFLSIGFITIAILATTVLLN--ISQASEKSTPQADSMHQASHKKVTNDNGKANKKVK?LGSRKFPS S . cohnii MLKNILVS- I I IGTLLFLSSAINA-EVQAQNQNDnlKSSQQANESKQVG- -- ------------TATPR * 10 20 30 40 50 60 70 I I I I S . aureus VILPNNPRHOITDTT_'GHYAPVTYIQVEAPTG--TFIASGVVVGKDTLLTN~'vVDATHGDPHJI. LK .ZI.FPSAI S . epidermidis VILPNN 'RHOIFKTTQGHYDAVSFIYIPIDGG--YI~SGSGVVVGENEILTN H,TVNGAKGNPRNISVHPSAK S . warneri VILPNNDRHOINDTTLGHYAPVTFVQVQSNEG--TFIASGVVVGKDKLLTN HrvDATHGKPRALKAFPSAV S . saprop.IJyticus WLPNDDRTQIE. TTNGHYQSVGYISIGDNIA------TGVVIDKNTVLTN H,T.l'NLSEGN---HNFSPJI.AQ S. caprae VI LPNNNRHQI SNTQEGHYAPVS FVK IYNDSGDLVASGSG IVVGEKE I LTN H IVDAJI.HN . PDNLGVAPSSK S . cohnii VNLPGENRHQIENTQSSHYQS IGY I EKGETIA- - - ---TGVVVGKNTVLTN TVNNGDGK --- LS FAP.ZI.AE * ** * ** * ** * * ***** * 80 90 100 110 120 130 140 I I I I I I I S . aureus QDNY PNGGFTAEQ ITKY SGEIlAI VKFS PNEQNKH I GEVVKPAT~·IS -NAETQVNQ I TVTGYPGlllill S . epidermidis ENDYP. GKFVGQEIIPYPGN AILRVSPNEIiNQIiIGQWKPATISSNTDT!UNEXITVTGYPG.QlS£1. S . warneri NQNNYP GGFTGEQITKYPGN~ IVKFSPNNQNQNIGEWTPATLSDNADTSQNQPITVTGYPGDKPL S . saprop.IJyticus NENTI·\PYGTFSEKEIEVYPGN ALlIiLNKNKDEQSVGD'NQPATLKDASAVTKDI1PITVTGYPGDKSL S. caprae SESEHPNGEFKGQEIKKYPGN SILKVQPNEDNKKIGDVVTPAKISSNSNTQTDQDITVTGYPG.QlS£1. S. cohnii . EKSFPYGTFTEKE\NAYPGD VLVHFNKNNEGQSVGDWTPATIGETSTVSSNDPITVTGYPGDKPL *'1'"******** * * * '* * * *: * 150 160 170 180 190 200 210 I I I I ! U I I I S . aUl.-eus ~SKGKITYLKGEAJolQYDLSTTGGISPVFNEKNEVIGIHNGGVPNEFNGJI'VFINENVR.!ti:I.lillNI S . epidel.-midis ATWilESVGKVVYIGGEELRYDLSTVGG S..,SPVFNGKNQVIGIHYGGVDNKYNSSVYINDFVQQFLRNNI
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