Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 398, Issue 1 (Jan 2017)

Issues

A novel plant enzyme with dual activity: an atypical Nudix hydrolase and a dipeptidyl peptidase III

Zrinka Karačić
  • Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bojana Vukelić
  • Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gabrielle H. Ho
  • Department of Plant and Microbial Biology, University of California, 461 Koshland Hall, Berkeley, CA 94720, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Iva Jozić
  • Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Iva Sučec
  • Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Branka Salopek-Sondi
  • Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Marija Kozlović
  • Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Steven E. Brenner
  • Department of Plant and Microbial Biology, University of California, 461 Koshland Hall, Berkeley, CA 94720, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jutta Ludwig-Müller
  • Institut für Botanik, Technische Universität Dresden, Zellescher Weg 20b, D-01062 Dresden, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Marija Abramić
  • Corresponding author
  • Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-07-28 | DOI: https://doi.org/10.1515/hsz-2016-0141

Abstract

In a search for plant homologues of dipeptidyl peptidase III (DPP III) family, we found a predicted protein from the moss Physcomitrella patens (UniProt entry: A9TLP4), which shared 61% sequence identity with the Arabidopsis thaliana uncharacterized protein, designated Nudix hydrolase 3. Both proteins contained all conserved regions of the DPP III family, but instead of the characteristic hexapeptide HEXXGH zinc-binding motif, they possessed a pentapeptide HEXXH, and at the N-terminus, a Nudix box, a hallmark of Nudix hydrolases, known to act upon a variety of nucleoside diphosphate derivatives. To investigate their biochemical properties, we expressed heterologously and purified Physcomitrella (PpND) and Arabidopsis (AtND) protein. Both hydrolyzed, with comparable catalytic efficiency, the isopentenyl diphosphate (IPP), a universal precursor for the biosynthesis of isoprenoid compounds. In addition, PpND dephosphorylated four purine nucleotides (ADP, dGDP, dGTP, and 8-oxo-dATP) with strong preference for oxidized dATP. Furthermore, PpND and AtND showed DPP III activity against dipeptidyl-2-arylamide substrates, which they cleaved with different specificity. This is the first report of a dual activity enzyme, highly conserved in land plants, which catalyzes the hydrolysis of a peptide bond and of a phosphate bond, acting both as a dipeptidyl peptidase III and an atypical Nudix hydrolase.

This article offers supplementary material which is provided at the end of the article.

Keywords: Arabidopsis thaliana; enzyme kinetics; metalloprotease; Physcomitrella patens; plant biochemistry; substrate specificity

References

  • Abramić, M., Zubanović, M., and Vitale, L. (1988). Dipeptidyl peptidase III from human erythrocytes. Biol. Chem. Hoppe-Seyler 369, 29–38.Google Scholar

  • Abramić, M., Schleuder, D., Dolovčak, L.J., Schröder, W., Strupat, K., Šagi, D., Peter-Katalinić, J., and Vitale, L. (2000). Human and rat dipeptidyl peptidase III: biochemical and mass spectrometric arguments for similarities and differences. Biol. Chem. 381, 1233–1243.Google Scholar

  • Abramić, M., Špoljarić, J., and Šimaga, Š. (2004). Prokaryotic homologs help to define consensus sequences in peptidase family M49. Period. biol. 106, 161–168.Google Scholar

  • Abramić, M., Karačić, Z., Šemanjski, M., Vukelić, B., and Jajčanin-Jozić, N. (2015). Aspartate 496 from the subsite S2 drives specificity of human dipeptidyl peptidase III. Biol. Chem. 396, 359–366.Google Scholar

  • Altschul, S.F., Madden, T.L., Schäffer, A.A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D.J. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402.Google Scholar

  • Baral, P.K., Jajčanin-Jozić, N., Deller, S., Macheroux, P., Abramić, M., and Gruber, K. (2008). The first structure of dipeptidyl-peptidase III provides insight into the catalytic mechanism and mode of substrate binding. J. Biol. Chem. 283, 22316–22324.Google Scholar

  • Baršun, M., Jajčanin, N., Vukelić, B., Špoljarić, J., and Abramić, M. (2007). Human dipeptidyl peptidase III acts as a post-proline-cleaving enzyme on endomorphins. Biol. Chem. 388, 343–348.Google Scholar

  • Berthelot, K., Estevez, Y., Deffieux, A., and Peruch, F. (2012). Isopentenyl diphosphate isomerase: a checkpoint to isoprenoid biosynthesis. Biochimie 94, 1621–1634.Google Scholar

  • Bessman, M.J., Frick, D.N., and O’Handley, S.F. (1996). The MutT proteins or “Nudix” hydrolases, a family of versatile, widely distributed, “housecleaning” enzymes. J. Biol. Chem. 271, 25059–25062.Google Scholar

  • Bezerra, G.A., Dobrovetsky, E., Viertlmayr, R., Dong, A., Binter, A., Abramić, M., Macheroux, P., Dhe-Paganon, S., and Gruber, K. (2012). Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III. Proc. Natl. Acad. Sci. USA 109, 6525–6530.Google Scholar

  • Bonanno, J.B., Edo, C., Eswar, N., Pieper, U., Romanowski, M.J., Ilyin, V., Gerchman, S.E., Kycia, H., Studier, F.W., Sali, A., et al. (2001). Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis. Proc. Natl. Acad. Sci. USA 98, 12986–12901.Google Scholar

  • Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254.Google Scholar

  • Chen, J.-M. and Barrett, A.J. (2004). Dipeptidyl-peptidase III. In: Handbook of Proteolytic Enzymes, Vol. 1, A.J. Barrett, N.D. Rawlings and J.F. Woessner, eds. (Amsterdam, The Netherlands: Elsevier Academic Press), pp. 809–812.Google Scholar

  • Chiba, T., Li, Y.-H., Yamane, T., Ogikubo, O., Fukuoka, M., Arai, R., Takahashi, S., Ohtsuka, T., Ohkubo, I., and Matsui, N. (2003). Inhibition of recombinant dipeptidyl peptidase III by synthetic hemorphin-like peptides. Peptides 24, 773–778.Google Scholar

  • Dunn, C.A., O’Handley, S.F., Frick, D.N., and Bessman, M.J. (1999). Studies on the ADP-ribose pyrophosphatase subfamily of the nudix hydrolases and tentative identification of trgB, a gene associated with tellurite resistance. J. Biol. Chem. 274, 32318–32324.Google Scholar

  • Ellis, S. and Nuenke, J.M. (1967). Dipeptidyl arylamidase III of the pituitary: purification and characterization. J. Biol. Chem. 242, 4623–4629.Google Scholar

  • Fukasawa, K., Fukasawa, K.M., Kanai, M., Fujii, S., Hirose, J., and Harada, M. (1998). Dipeptidyl peptidase III is a zinc metallo-exopeptidase: molecular cloning and expression. Biochem. J. 329, 275–282.Google Scholar

  • Fukasawa, K., Fukasawa, K.M., Iwamoto, H., Hirose, J., and Harada, M. (1999). The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc coordination and the catalytic activity of the enzyme. Biochemistry 38, 8299–8303.Google Scholar

  • Geer, L.Y., Domrachev, M., Lipman, D.J., and Bryant S.H. (2002). CDART: protein homology by domain architecture. Genome Res. 12, 1619–1623.Google Scholar

  • George, K.W., Alonso-Gutierrez, J., Keasling, J.D., and Lee, T.S. (2015). Isoprenoid drugs, biofuels, and chemicals – Artemisinin, farnesene, and beyond. Adv. Biochem. Eng. Biotechnol. 148, 355–389.Google Scholar

  • Gunawardana, D., Likic, V.A., and Gayler, K.R. (2009). A comprehensive bioinformatics analysis of the nudix superfamily in Arabidopsis thaliana. Comp. Funct. Genom. 2009, Article Number: 820381.Google Scholar

  • Hast, B.E., Goldfarb, D., Mulvaney, K.M., Hast, M.A., Siesser, P.F., Yan, F., Hayes, D.N., and Major, M.B. (2013). Proteomic analysis of ubiquitin ligase KEAP1 reveals associated proteins that inhibit NRF2 ubiquitination. Cancer Res. 73, 2199–2210.Google Scholar

  • Henry, L.K., Gutensohn, M., Thomas, S.T., Noel, J.P., and Dudareva, N. (2015). Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid production in plants. Proc. Natl. Acad. Sci. USA 112, 10050–10055.Google Scholar

  • Hoshino, T. and Egushi T. (2007). Functional analysis of type 1 isopentenyl diphosphate isomerase from Halobacterium sp. NRC-1. Biosci. Biotechnol. Biochem. 71, 2588–2591.Google Scholar

  • Jajčanin-Jozić, N., Deller, S., Pavkov, T., Macheroux, P., and Abramić, M. (2010). Identification of the reactive cysteine residues in yeast dipeptidyl peptidase III. Biochimie 92, 89–96.Google Scholar

  • Jajčanin-Jozić, N. and Abramić, M. (2013). Hydrolysis of dipeptide derivatives reveals the diversity in the M49 family. Biol. Chem. 394, 767–771.Google Scholar

  • Kansanen, E., Kuosmanen, S.M., Leinonen, H., and Levonen A.-L. (2013). The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol. 1, 45–49.Google Scholar

  • Karačić, Z., Špoljarić, J., Rožman, M., and Abramić, M. (2012). Molecular determinants of human dipeptidyl peptidase sensitivity to thiol modifying reagents. Biol. Chem. 393, 1523–1532.Google Scholar

  • Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.Google Scholar

  • Liu, Y., Kern, J.T., Walker, J.R., Johnson, J.A., Schultz, P.G., and Luesch, H. (2007). A genomic screen for activators of the antioxidant response element. Proc. Natl. Acad. Sci. USA 104, 5205–5210.CrossrefGoogle Scholar

  • Magnard, J.-L., Roccia, A., Caissard, J.-C., Vergne, P., Sun, P., Hecquet R., Dubois, A., Hibrand-Saint Oyant L., Jullien, F., Nicolè, F., et al. (2015). Biosynthesis of monoterpene scent compounds in roses. Science 349, 81–83.Google Scholar

  • McLennan, A.G. (2006). Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both? Cell. Mol. Life Sci. 70, 373–385.Google Scholar

  • Mildvan, A.S., Xia, Z., Azurmendi, H.F., Saraswat, V., Legler, P.M., Massiah, M.A., Gabelli, S.B., Bianchet, M.A., Kang, L.-W., and Amzel, L.M. (2005). Structures and mechanisms of Nudix hydrolases. Arch. Biochem. Biophys. 433, 129–143.Google Scholar

  • Müller, S.J., Gütle, D.D., Jacquot, J.-P., and Reski, R. (2015). Can mosses serve as model organisms for forest research? Ann. For. Sci. 468.Google Scholar

  • Ogawa, T., Ueda, Y., Yoshimura, K., and Shigeoka, S. (2005). Comprehensive analysis of cytosolic nudix hydrolases in Arabidopsis thaliana. J. Biol. Chem. 280, 25277–25283.Google Scholar

  • Ogawa, T., Yoshimura, K., Miyake, H., Ishikawa, K., Ito, D., Tanabe, N., and Shigeoka, S. (2008). Molecular characterization of organelle-type Nudix hydrolases in Arabidopsis. Plant Physiol. 148, 1412–1424.Google Scholar

  • Prigge, M.J. and Bezanilla, M. (2010). Evolutionary crossroads in developmental biology: Physcomitrella patens. Development 137, 3535–3543.Google Scholar

  • Rawlings, N.D., Waller, M., Barrett, A.J., and Bateman, A. (2014). MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 42, D503–D509.Google Scholar

  • Rensing, S.A., Lang, D., Zimmer, A.D., Terry, A., Salamov, A., Shapiro H, Nishiyama T, Perroud PF, Lindquist EA, Kamisugi Y., et al., (2008). The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants. Science 319, 64–69.Google Scholar

  • Salopek-Sondi, B., Vukelić, B., Špoljarić, J., Šimaga, Š., Vujaklija, D., Makarević, J., Jajčanin, N., and Abramić, M. (2008). Functional tyrosine residue in the active center of human dipeptidyl peptidase III. Biol. Chem. 389, 163–167.Google Scholar

  • Schaller, A. (2004). A cut above the rest: the regulatory function of plant proteases. Planta 220, 183–197.Google Scholar

  • Sievers, F., Wilm, A., Dineen, D.G., Gibson, T.J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Söding, J., et al. (2011). Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst Biol. 7, 539. doi:.CrossrefGoogle Scholar

  • Špoljarić, J., Salopek-Sondi, B., Makarević, J., Vukelić, B., Agić, D., Šimaga, Š., Jajčanin-Jozić, N., and Abramić, M. (2009). Absolutely conserved tryptophan in M49 family of peptidases contributes to catalysis and binding of competitive inhibitors. Bioorg. Chem. 37, 70–76.Google Scholar

  • The UniProt Consortium. Ongoing and future developments at the Universal Protein Resource. (2011). Nucleic Acids Res. 39, D214–D219.Google Scholar

  • Vukelić, B., Salopek-Sondi, B., Špoljarić, J., Sabljić, I., Meštrović, N., Agić, D., and Abramić, M. (2012). Reactive cysteine in the active-site motif of Bacteroides thetaiotaomicron dipeptidyl peptidase III is a regulatory residue for enzyme activity. Biol. Chem. 393, 37–46.Google Scholar

  • Wang, Y., Qiu, C., Zhang, F., Guo, B., Miao, Z., Sun, X., and Tang, K. (2009). Molecular cloning, expression profiling and functional analyses of a cDNA encoding isopentenyl diphosphate isomerase from Gossypium barbadense. Biosci. Rep. 29, 111–119.Google Scholar

  • Wouters, J., Oudjama, Y., Barkley, S.J., Tricot, C., Stalon, V., Droogmans, L., and Poulter, C.J. (2003). Catalytic mechanism of Escherichia coli isopentenyl diphosphate isomerase involves Cys-67, Glu-116, and Tyr-104 as suggested by crystal structures of complexes with transition state analogues and irreversible inhibitors. J. Biol. Chem. 278, 11903–11908.Google Scholar

  • Xu, W., Dunn, C.A., O’Handley, S.F., Smith, D.L., and Bessman, M.J. (2006). Three new nudix hydrolases from Escherichia coli. J. Biol. Chem. 281, 22794–22798.Google Scholar

  • Xu, A., Desai, A.M., Brenner, S.E., and Kirsch, J.F. (2013). A continuous fluorescence assay for the characterization of Nudix hydrolases. Anal. Biochem. 437, 178–184.Google Scholar

  • Yamada, K., Lim, J., Dale, J.M., Chen, H., Shinn, P., Palm C.J., Southwick, A.M., Wu, H.C., Kim, C., Nguyen, M., et al., (2003). Empirical analysis of transcriptional activity in the Arabidosis Genome. Science 302, 842–846.Google Scholar

  • Yoshimura, K. and Shigeoka, S. (2015). Versatile physiological functions of the Nudix hydrolase family in Arabidopsis. Biosci. Biotech. Bioch. 79, 354–366.Google Scholar

  • Zhang, C., Liu, L., Xu, H., Wei, Z., Wang, Y., Lin, Y., and Gong, W. (2007). Crystal structures of human IPP isomerase: new insights into the catalytic mechanism. J. Mol. Biol. 366, 1437–1446.Google Scholar

About the article

Received: 2016-02-20

Accepted: 2016-07-25

Published Online: 2016-07-28

Published in Print: 2017-01-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2016-0141.

Export Citation

©2017 Walter de Gruyter GmbH, Berlin/Boston. Copyright Clearance Center

Supplementary Article Materials

Comments (0)

Please log in or register to comment.
Log in