Abstract
The primary structures of the full-length precursors of thermolysin-like proteinases (TLPs) were systemically analyzed. Structural comparison of the precursor amino-terminal regions (ATRs) removed during maturation allowed us to divide the family into two groups: peptidases with short (about 50 amino acids) and long (about 200 amino acids) ATRs. The accumulation of mutations in the ATRs of both types proved to correlate with that in the catalytic domains. No classical signal peptides were identified in the short ATRs, but they contained a conserved PPL-motif near the initiation methionine. The functional role of the short ATRs and PPL-motif is currently unclear. The C-terminal regions (CTRs) of TLP precursors, which are often removed during maturation, too, are found in about a half of precursors with long ATRs, but occur more rarely in precursors with short ATRs. CTRs in TLP precursors contain previously identified conserved domains typical for many other proteins and likely underlie the interaction with high molecular weight substrates.
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Notes
The current MEROPS database (release 7.70) was supplemented by new M4 peptidase sequences. Each of these sequences was analyzed individually. The results of the analysis are summarized in the footnotes to Table 1.
Abbreviations
- TLP:
-
Thermolysin-like proteinase
- ATR:
-
Amino-terminal region
- CTR:
-
Carboxy-terminal region
References
Rawlings ND, Barrett AJ (1995) Methods Enzymol 248:183–228
Rawlings ND, Morton FR, Barrett AJ (2006) Nucleic Acids Res 34:D270–272
Matthews BW (1988) Acc Chem Res 21:333–340
de Kreij A, Venema G, van den Burg B (2000) J Biol Chem 275:31115–31120
Feder J (1967) Biochemistry 6:2088–2093
Feder J, Schuck JM (1970) Biochemistry 9:2784–2791
Schechter I, Berger A (1967) Biochem Biophys Res Commun 27:157–162
Shinde U, Inouye M (2000) Semin Cell Dev Biol 11:35–44
Braun P, Tommassen J, Filloux A (1996) Mol Microbiol 19:297–306
Marie-Claire C, Ruffet E, Beaumont A, Roques BP (1999) J Mol Biol 285:1911–1915
McIver KS, Kessler E, Olson JC, Ohman DE (1995) Mol Microbiol 18:877–889
Tang B, Nirasawa S, Kitaoka M, Marie-Claire C, Hayashi K (2003) Biochem Biophys Res Commun 301:1093–1098
Kessler E, Safrin M (1994) J Biol Chem 269:22726–22731
O’Donohue MJ, Roques BP, Beaumont A (1994) Biochem J 300(Pt 2):599–603
Serkina AV, Gorozhankina TF, Shevelev AB, Chestukhina GG (1999) FEBS Lett 456:215–219
Wetmore DR, Wong SL, Roche RS (1992) Mol Microbiol 6:1593–1604
Kearns DB, Bonner PJ, Smith DR, Shimkets LJ (2002) J Bacteriol 184:1678–1684
Miyamoto K, Nukui E, Hirose M, Nagai F, Sato T, Inamori Y, Tsujibo H (2002) Appl Environ Microbiol 68:5563–5570
Miyamoto K, Tsujibo H, Nukui E, Itoh H, Kaidzu Y, Inamori Y (2002) Biosci Biotechnol Biochem 66:416–421
Miyoshi S, Kawata K, Tomochika K, Shinoda S, Yamamoto S (2001) Toxicon 39:1883–1886
Miyoshi S, Wakae H, Tomochika K, Shinoda S (1997) J Bacteriol 179:7606–7609
Demidyuk IV, Kalashnikov AE, Gromova TY, Gasanov EV, Safina DR, Zabolotskaya MV, Rudenskaya GN, Kostrov SV (2006) Protein Expr Purif 47:551–561
Zabolotskaya MV, Demidyuk IV, Akimkina TV, Kostrov SV (2004) Protein J 23:483–492
Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) Nucleic Acids Res 25:4876–4882
Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) J Mol Biol 340:783–795
Schneider TD, Stephens RM (1990) Nucleic Acids Res 18:6097–6100
Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) Genome Res 14:1188–1190
Felsenstein J (2005) PHYLIP (Phylogeny Inference Package) version 3.6. Distributed by the author. Department of Genome Sciences, University of Washington, Seattle
O’Donohue MJ, Beaumont A (1996) J Biol Chem 271:26477–26481
Tang B, Nirasawa S, Kitaoka M, Hayashi K (2002) Biochim Biophys Acta 1596:16–27
Tang B, Nirasawa S, Kitaoka M, Hayashi K (2002) Biochem Biophys Res Commun 296:78–84
Mansfeld J, Petermann E, Durrschmidt P, Ulbrich-Hofmann R (2005) Protein Expr Purif 39:219–228
Braun P, Bitter W, Tommassen J (2000) Microbiology 146(Pt 10):2565–2572
Marie-Claire C, Roques BP, Beaumont A (1998) J Biol Chem 273:5697–5701
McIver K, Kessler E, Ohman DE (1991) J Bacteriol 173:7781–7789
Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer EL, Studholme DJ, Yeats C, Eddy SR (2004) Nucleic Acids Res 32:D138–141
McIver KS, Kessler E, Ohman DE (2004) Microbiology 150:3969–3977
Yeats C, Rawlings ND, Bateman A (2004) Trends Biochem Sci 29:169–172
Kyostio SR, Cramer CL, Lacy GH (1991) J Bacteriol 173:6537–6546
Kwon YT, Lee HH, Rho HM (1993) Gene 125:75–80
Novikova SI, Serkina AV, Konstantinova GE, Khlebalina OI, Chestukhina GG, Shevelev AB (2001) Vopr Med Khim 47:123–131
Shinde U, Fu X, Inouye M (1999) J Biol Chem 274:15615–15621
Shinde UP, Liu JJ, Inouye M (1997) Nature 389:520–522
Yasuda Y, Tsukuba T, Okamoto K, Kadowaki T, Yamamoto K (2005) J Biochem (Tokyo) 138:621–630
Hase CC, Finkelstein RA (1990) Infect Immun 58:4011–4015
Kato JY, Suzuki A, Yamazaki H, Ohnishi Y, Horinouchi S (2002) J Bacteriol 184:6016–6025
Lee SO, Kato J, Nakashima K, Kuroda A, Ikeda T, Takiguchi N, Ohtake H (2002) Biosci Biotechnol Biochem 66:1366–1369
Nirasawa S, Nakajima Y, Zhang ZZ, Yoshida M, Hayashi K (1999) Biochem J 341(Pt 1):25–31
Norqvist A, Norrman B, Wolf-Watz H (1990) Infect Immun 58:3731–3736
Oda K, Okayama K, Okutomi K, Shimada M, Sato R, Takahashi S (1996) Biosci Biotechnol Biochem 60:463–467
Chuang YC, Chang TM, Chang MC (1997) Gene 189:163–168
Miyoshi N, Shimizu C, Miyoshi S, Shinoda S (1987) Microbiol Immunol 31:13–25
Miyoshi S, Sonoda Y, Wakiyama H, Rahman MM, Tomochika K, Shinoda S, Yamamoto S, Tobe K (2002) Microb Pathog 33:127–134
David VA, Deutch AH, Sloma A, Pawlyk D, Ally A, Durham DR (1992) Gene 112:107–112
Teo JW, Zhang LH, Poh CL (2003) Gene 303:147–156
Behmlander RM, Dworkin M (1994) J Bacteriol 176:6295–6303
Matsushita O, Koide T, Kobayashi R, Nagata K, Okabe A (2001) J Biol Chem 276:8761–8770
Toyoshima T, Matsushita O, Minami J, Nishi N, Okabe A, Itano T (2001) Connect Tissue Res 42:281–290
Creemers JW, Siezen RJ, Roebroek AJ, Ayoubi TA, Huylebroeck D, Van de Ven WJ (1993) J Biol Chem 268:21826–21834
Gluschankof P, Fuller RS (1994) EMBO J 13:2280–2288
Rovere C, Luis J, Lissitzky JC, Basak A, Marvaldi J, Chretien M, Seidah NG (1999) J Biol Chem 274:12461–12467
Creemers JW, Usac EF, Bright NA, Van de Loo JW, Jansen E, Van de Ven WJ, Hutton JC (1996) J Biol Chem 271:25284–25291
Lusson J, Benjannet S, Hamelin J, Savaria D, Chretien M, Seidah NG (1997) Biochem J 326(Pt 3):737–744
Taylor NA, Shennan KI, Cutler DF, Docherty K (1997) Biochem J 321(Pt 2):367–373
Ueda K, Lipkind GM, Zhou A, Zhu X, Kuznetsov A, Philipson L, Gardner P, Zhang C, Steiner DF (2003) Proc Natl Acad Sci USA 100:5622–5627
Zhou A, Martin S, Lipkind G, LaMendola J, Steiner DF (1998) J Biol Chem 273:11107–11114
Zhu X, Muller L, Mains RE, Lindberg I (1998) J Biol Chem 273:1158–1164
Acknowledgments
This work was supported by the Russian Foundation for Basic Research (project nos. 06-04-48678, 06-04-48690, and 06-04-08123).
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Demidyuk, I.V., Gasanov, E.V., Safina, D.R. et al. Structural Organization of Precursors of Thermolysin-like Proteinases. Protein J 27, 343–354 (2008). https://doi.org/10.1007/s10930-008-9143-2
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DOI: https://doi.org/10.1007/s10930-008-9143-2