Abstract
The lysosomal lumen contains numerous acidic hydrolases involved in the degradation of carbohydrates, lipids, proteins, and nucleic acids, which are basic cell components that turn over continuously within the cell and/or are ingested from outside of the cell. Deficiency in almost any of these hydrolases causes accumulation of the undigested material in secondary lysosomes, which manifests itself as a form of lysosomal storage disorder (LSD). Mutations in tripeptidyl-peptidase I (TPP I) underlie the classic late-infantile form of neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative disorders of childhood. TPP I is an aminopeptidase with minor endopeptidase activity and Ser475 serving as an active-site nucleophile. The enzyme is synthesized as a highly glycosylated precursor transported by mannose-6-phosphate receptors to lysosomes, where it undergoes proteolytic maturation. This review summarizes recent progress in understanding of TPP I biology and molecular pathology of the CLN2 disease process, including distribution of the enzyme, its biosynthesis, glycosylation, transport and activation, as well as catalytic mechanisms and their potential implications for pathogenesis and treatment of the underlying disease. Promising data from gene and stem cell therapy in laboratory animals raise hope that CLN2 will be the first neurodegenerative LSD for which causative treatment will become available for humans.
References
Altorjay, A., Paal, B., Sohar, N., Kiss, J., Szanto, I., and Sohar, I. (2005). Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus. World J. Gastroenterol.11, 5751–5756.10.3748/wjg.v11.i37.5751Search in Google Scholar
Andersen, K.J. and McDonald, J.K. (1987). Subcellular distribution of renal tripeptide-releasing exopeptidases active on collagen-like sequences. Am. J. Physiol.252, F890–F898.10.1152/ajprenal.1987.252.5.F890Search in Google Scholar
Asano, N., Ishii, S., Kizu, H., Ikeda, K., Yasuda, K., Kato, A., Martin, O.R., and Fan, J.Q. (2000). In vitro inhibition and intracellular enhancement of lysosomal α-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives. Eur. J. Biochem.267, 4179– 4186.10.1046/j.1432-1327.2000.01457.xSearch in Google Scholar
Bernardini, F. and Warburton, M.J. (2001). The substrate range of tripeptidyl-peptidase I. Eur. J. Paediatr. Neurol.5 (Suppl. A), 69–72.10.1053/ejpn.2000.0438Search in Google Scholar
Bienkowski, M.J. and Conrad, H.E. (1984). Kinetics of proteoheparan sulfate synthesis, secretion, endocytosis, and catabolism by a hepatocyte cell line J. Biol. Chem.259, 12989–12996.10.1016/S0021-9258(18)90645-9Search in Google Scholar
Brady, R.O. (2006). Enzyme replacement for lysosomal diseases. Annu. Rev. Med.57, 283–296.10.1146/annurev.med.57.110104.115650Search in Google Scholar PubMed
Chen, R., Fearnley, I.M., Palmer, D.N., and Walker, J.E. (2004). Lysine 43 is trimethylated in subunit C from bovine mitochondrial ATP synthase and in storage bodies associated with Batten disease. J. Biol. Chem.279, 21883–21887.10.1074/jbc.M402074200Search in Google Scholar PubMed
Crystal, R.G., Sondhi, D., Hackett, N.R., Kaminsky, S.M., Worgall, S., Stieg, P., Souweidane, M., Hosain, S., Heier, L., Ballon, D., et al. (2004). Clinical protocol. Administration of a replication-deficient adeno-associated virus gene transfer vector expressing the human CLN2 cDNA to the brain of children with late infantile neuronal ceroid lipofuscinosis. Hum. Gene Ther.15, 1131–1154.Search in Google Scholar
Dekaban, A.S. (1978). Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann. Neurol.4, 345–356.10.1002/ana.410040410Search in Google Scholar PubMed
Du, P.G., Kato, S., Li, Y.H., Maeda, T., Yamane, T., Yamamoto, S., Fujiwara, M., Yamamoto, Y., Nishi, K., and Ohkubo, I. (2001). Rat tripeptidyl peptidase I: molecular cloning, functional expression, tissue localization and enzymatic characterization. Biol. Chem.382, 1715–1725.10.1515/BC.2001.207Search in Google Scholar PubMed
Elleder, M., Sokolova, J., and Hrebicek, M. (1997). Follow-up study of subunit C of mitochondrial ATP synthase (SCMAS) in Batten disease and in unrelated lysosomal disorders. Acta Neuropathol. (Berl.)93, 379–390.10.1007/s004010050629Search in Google Scholar PubMed
Ezaki, J., Tanida, I., Kanehagi, N., and Kominami, E. (1999). A lysosomal proteinase, the late infantile neuronal ceroid lipofuscinosis gene (CLN2) product, is essential for degradation of a hydrophobic protein, the subunit C of ATP synthase. J. Neurochem.72, 2573–2582.10.1046/j.1471-4159.1999.0722573.xSearch in Google Scholar PubMed
Ezaki, J., Takeda-Ezaki, M., Oda, K., and Kominami, E. (2000). Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis. Biochem. Biophys. Res. Commun.268, 904–908.10.1006/bbrc.2000.2207Search in Google Scholar PubMed
Gaillard, P.J., Visser, C.C., and de Boer, A.G. (2005). Targeted delivery across the blood-brain barrier. Expert Opin. Drug Deliv.2, 299–309.10.1517/17425247.2.2.299Search in Google Scholar PubMed
Golabek, A.A., Kida, E., Walus, M., Wujek, P., Mehta, P., and Wisniewski, K.E. (2003). Biosynthesis, glycosylation and enzymatic processing in vivo of human tripeptydyl-peptidase I. J. Biol. Chem.278, 7135–7145.10.1074/jbc.M211872200Search in Google Scholar PubMed
Golabek, A.A., Wujek, P., Walus, M., Bieler, S., Soto, C., Wisniewski, K.E., and Kida, E. (2004). Maturation of human tripeptidyl-peptidase I in vitro. J. Biol. Chem.279, 31058–31067.10.1074/jbc.M400700200Search in Google Scholar PubMed
Golabek, A.A., Walus, M., Wisniewski, K.E., and Kida, E. (2005). Glycosaminoglycans modulate activation, activity, and stability of tripeptidyl-peptidase I in vitro and in vivo. J. Biol. Chem.280, 7550–7561.10.1074/jbc.M412047200Search in Google Scholar PubMed
Guo, H., Wlodawer, A., and Guo, H. (2005). A general acid-base mechanism for the stabilization of a tetrahedral adduct in a serine-carboxyl peptidase: a computational study. J. Am. Chem. Soc.127, 15662–15663.10.1021/ja0520565Search in Google Scholar PubMed
Hackett, N.R., Redmond, D.E., Sondhi, D., Giannaris, E.L., Vassallo, E., Stratton, J., Qiu, J., Kaminsky, S.M., Lesser, M.L., Fisch, G.S., et al. (2005). Safety of direct administration of AAV2(CU)hCLN2, a candidate treatment for the central nervous system manifestations of late infantile neuronal ceroid lipofuscinosis, to the brain of rats and nonhuman primates. Hum. Gene Ther.16, 1484–1503.10.1089/hum.2005.16.1484Search in Google Scholar PubMed
Haskell, R.E., Hughes, S.M., Chiorini, J.A,. Alisky, J.M., and Davidson, B.L. (2003). Viral-mediated delivery of the late-infantile neuronal ceroid lipofuscinosis gene, TPP-I to the mouse central nervous system. Gene Ther.10, 34–42.10.1038/sj.gt.3301843Search in Google Scholar PubMed
Helenius, A. and Aebi, M. (2004). Roles of N-linked glycans in the endoplasmic reticulum. Annu. Rev. Biochem.73, 1019–1049.10.1146/annurev.biochem.73.011303.073752Search in Google Scholar PubMed
Iozzo, R.V. (1998). Matrix proteoglycans: from molecular design to cellular function. Annu. Rev. Biochem.67, 609–652.10.1146/annurev.biochem.67.1.609Search in Google Scholar
Jeyakumar, M., Dwek, R.A., Butters, T.D., and Platt, F.M. (2005). Storage solutions: treating lysosomal disorders of the brain. Nat. Rev. Neurosci.6, 713–725.10.1038/nrn1725Search in Google Scholar
Junaid, M.A. and Pullarkat, R.K. (1999). Increased brain lysosomal pepstatin-insensitive proteinase activity in patients with neurodegenerative diseases. Neurosci. Lett.264, 157–160.10.1016/S0304-3940(99)00095-6Search in Google Scholar
Junaid, M.A., Clark, G.M., and Pullarkat, R.K. (2000a). A lysosomal pepstatin-insensitive proteinase as a novel biomarker for breast carcinoma. Int. J. Biol. Markers15, 129–134.10.1177/172460080001500201Search in Google Scholar
Junaid, M.A., Wu, G., and Pullarkat, R.K. (2000b). Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. J. Neurochem.74, 287–294.10.1046/j.1471-4159.2000.0740287.xSearch in Google Scholar
Kelly, S., Bliss, T.M., Shah, A.K., Sun, G.H., Ma, M., Foo, W.C., Masel, J., Yenari, M.A., Weissman, I.L., Uchida, N., et al. (2004). Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex. Proc. Natl. Acad. Sci. USA101, 11839–11844.10.1073/pnas.0404474101Search in Google Scholar
Kida, E., Wisniewski, K.E., and Golabek, A.A. (1993). Increased expression of subunit C of mitochondrial ATP synthase in brain tissue from neuronal ceroid lipofuscinoses and mucopolysaccharidosis cases but not in long-term fibroblast cultures. Neurosci. Lett.164, 121–124.10.1016/0304-3940(93)90872-ISearch in Google Scholar
Kida, E., Golabek, A.A., and Wisniewski, K. (2001a). Cellular pathology and pathogenic aspects of neuronal ceroid lipofuscinoses. Adv. Genet.45, 35–66.10.1016/S0065-2660(01)45003-6Search in Google Scholar
Kida, E., Golabek, A.A., Walus, M., Wujek, P., Kaczmarski, W., and Wisniewski, K.E. (2001b). Distribution of tripeptidyl peptidase I in human tissues under normal and pathological conditions. J. Neuropathol. Exp. Neurol.60, 280–292.10.1093/jnen/60.3.280Search in Google Scholar PubMed
Koike, M., Shibata, M., Ohsawa, Y., Kametaka, S., Waguri, S., Kominami, E., and Uchiyama, Y. (2002). The expression of tripeptidyl peptidase I in various tissues of rats and mice. Arch. Histol. Cytol.65, 219–232.10.1679/aohc.65.219Search in Google Scholar PubMed
Kopan, S., Sivasubramaniam, U., and Warburton, M.J. (2004). The lysosomal degradation of neuromedin B is dependent on tripeptidyl peptidase-I: evidence for the impairment of neuropeptide degradation in late-infantile neuronal ceroid lipofuscinosis. Biochem. Biophys. Res. Commun.319, 58–65.10.1016/j.bbrc.2004.04.142Search in Google Scholar
Kraemer, P.M. (1971). Heparan sulfates of cultured cells. I. Membrane-associated and cell-sap species in Chinese hamster cells. Biochemistry10, 1437–1445.Search in Google Scholar
Kurachi, Y., Oka, A., Itoh, M., Mizuguchi, M., Hayashi, M., and Takashima, S. (2001). Distribution and development of CLN2 protein, the late-infantile neuronal ceroid lipofuscinosis gene product. Acta Neuropathol. (Berl.)102, 20–26.10.1007/s004010000321Search in Google Scholar
Li, Z., Yasuda, Y., Li, W., Bogyo, M., Katz, N., Gordon, R.E., Fields, G.B., and Bromme, D. (2004). Regulation of collagenase activities of human cathepsins by glycosaminoglycans. J. Biol. Chem.279, 5470–5479.10.1074/jbc.M310349200Search in Google Scholar
Lin, L. and Lobel, P. (2001). Production and characterization of recombinant human CLN2 protein for enzyme-replacement therapy in late infantile neuronal ceroid lipofuscinosis. Biochem. J.357, 49–55.10.1042/bj3570049Search in Google Scholar
Lin, L., Sohar, I., Lackland, H., and Lobel, P. (2001). The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. J. Biol. Chem.276, 2249–2255.10.1074/jbc.M008562200Search in Google Scholar
Liu, C-G., Sleat, D.E., Donnelly, R.J., and Lobel, P. (1998). Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis. Genomics50, 206–212.10.1006/geno.1998.5328Search in Google Scholar
McDonald, J.K., Hoisington, A.R., and Eisenhauer, D.A. (1985). Partial purification and characterization of an ovarian tripeptidyl peptidase: a lysosomal exopeptidase that sequentially releases collagen-related (Gly-Pro-X) triplets. Biochem. Biophys. Res. Commun.126, 63–71.10.1016/0006-291X(85)90571-6Search in Google Scholar
Mellman, I., Fuchs, R., and Helenius, A. (1986). Acidification of the endocytic and exocytic pathways. Annu. Rev. Biochem.55, 663–700.10.1146/annurev.bi.55.070186.003311Search in Google Scholar PubMed
Mikhailenko, I., Kounnas, M.Z., and Strickland, D.K. (1995). Low density lipoprotein receptor-related protein/α2-macroglobulin receptor mediates the cellular internalization and degradation of thrombospondin. A process facilitated by cell-surface proteoglycans. J. Biol. Chem.270, 9543–9549.10.1074/jbc.270.16.9543Search in Google Scholar PubMed
Mortimore, G. (1987). Mechanism and regulation of induced and basal protein degradation in liver. In: Lysosomes: Their Role in Protein Breakdown, H. Glaumann and F.J. Ballard, eds. (New York, USA: Academic Press), pp. 415–444.Search in Google Scholar
Neuwelt, E.A., Howieson, J., Frenkel, E.P., Specht, H.D., Weigel, R., Buchan, C.G., and Hill, S.A. (1986). Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma. Neurosurgery19, 573–582.10.1227/00006123-198610000-00011Search in Google Scholar PubMed
Ohkuma, S. and Poole, B. (1978). Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc. Natl. Acad. Sci. USA75, 3327–3331.10.1073/pnas.75.7.3327Search in Google Scholar
Oyama, H., Fujisawa, T., Suzuki, T., Dunn, B.M., Wlodawer, A., and Oda, K. (2005). Catalytic residues and substrate specificity of recombinant human tripeptidyl peptidase I (CLN2). J. Biochem. (Tokyo)138, 127–134.10.1093/jb/mvi110Search in Google Scholar
Page, A.E., Fuller, K., Chambers, T.J., and Warburton, M.J. (1993). Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption. Arch. Biochem. Biophys.306, 354–359.10.1006/abbi.1993.1523Search in Google Scholar
Palmer, D.N., Fearnley, I.M., Walker, J.E., Hall, N.A., Lake, B.D., Wolfe, L.S., Haltia, M., Martinus, R.D., and Jolly, R.D. (1992). Mitochondrial ATP synthase subunit C storage in the ceroid-lipofuscinoses (Batten disease). Am. J. Med. Genet.42, 561–567.10.1002/ajmg.1320420428Search in Google Scholar
Passini, M.A., Dodge, J.C., Bu, J., Yang, W., Zhao, Q., Sondhi, D., Hackett, N.R., Kaminsky, S.M., Mao, Q., Shihabuddin, L.S., et al. (2006). Intracranial delivery of CLN2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis. J. Neurosci.26, 1334–1342.10.1523/JNEUROSCI.2676-05.2006Search in Google Scholar
Rawlings, N.D. and Barrett, A.J. (1994). Families of serine peptidases. Methods Enzymol.244, 19–61.10.1016/0076-6879(94)44004-2Search in Google Scholar
Rawlings, N.D. and Barrett, A.J. (1999). Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late-infantile neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta1429, 496–500.10.1016/S0167-4838(98)00238-6Search in Google Scholar
Reiland, J. and Rapraeger, A.C. (1993). Heparan sulfate proteoglycan and FGF receptor target basic FGF to different intracellular destinations. J. Cell Sci.105, 1085–1093.10.1242/jcs.105.4.1085Search in Google Scholar PubMed
Robert, J., Auzan, C., Ventura, M.A., and Clauser, E. (2005). Mechanisms of cell-surface rerouting of an ER-retained mutant of the vasopressin V1b/V3 receptor by a pharmacological chaperone. J. Biol. Chem.280, 42198–42206.10.1074/jbc.M510180200Search in Google Scholar PubMed
Römisch, K. (2004). A cure for traffic jams: small molecule chaperones in the endoplasmic reticulum. Traffic5, 815–820.10.1111/j.1600-0854.2004.00231.xSearch in Google Scholar PubMed
Schueler, U.H., Kolter, T., Kaneski, C.R., Zirzow, G.C., Sandhoff, K., and Brady R.O. (2004). Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease. J. Inherit. Metab. Dis.27, 649–658.10.1023/B:BOLI.0000042959.44318.7cSearch in Google Scholar
Sharp, J.D., Wheeler, R.B., Lake, B.D., Savukoski, M., Jarvela, I.E., Peltonen, L., Gardiner, R.M., and Williams, R.E. (1997). Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11p15 and 15q21-23. Hum. Mol. Genet.6, 591–595.10.1093/hmg/6.4.591Search in Google Scholar PubMed
Sleat, D.E., Donnelly, R.J., Lackland H., Liu, C.G., Sohar, I., Pullarkat, R.K., and Lobel, P. (1997). Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science277, 1802–1805.10.1126/science.277.5333.1802Search in Google Scholar PubMed
Sleat, D.E., Gin, R.M., Sohar, I., Wisniewski, K.E., Sklower Brooks, S., Pullarkat, R., Palmer, D.N., Lerner, T.J., Boustany, R.M., Uldall, P., et al. (1999). Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Am. J. Hum. Genet.64, 1511–1523.10.1086/302427Search in Google Scholar PubMed PubMed Central
Sleat, D.E., Sohar, I., Gin, R.M., and Lobel, P. (2001). Aminoglycoside-mediated suppression of nonsense mutations in late infantile neuronal ceroid lipofuscinosis. Eur. J. Paediatr. Neurol.5 (Suppl. A), 57–62.10.1053/ejpn.2000.0436Search in Google Scholar PubMed
Sleat, D.E., Wiseman, J.A., El-Banna, M., Kim, K.H., Mao, Q., Price, S., Macauley, S.L., Sidman, R.L., Shen, M.M., Zhao, Q., et al. (2004). A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration. J. Neurosci.24, 9117–9126.10.1523/JNEUROSCI.2729-04.2004Search in Google Scholar PubMed PubMed Central
Sohar, N., Sohar, I., and Hammer, H. (2005). Lysosomal enzyme activities: new potential markers for Sjögren's syndrome. Clin. Biochem.38, 1120–1126.10.1016/j.clinbiochem.2005.09.003Search in Google Scholar PubMed
Steinfeld, R., Steinke, H.B., Isbrandt, D., Kohlschutter, A., and Gartner, J. (2004). Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes. Hum. Mol. Genet.13, 2483–2491.10.1093/hmg/ddh264Search in Google Scholar PubMed
Suopanki, J., Partanen, S., Ezaki, J., Baumann, M., Kominami, E., and Tyynela J. (2000). Developmental changes in the expression of neuronal ceroid lipofuscinoses-linked proteins. Mol. Genet. Metab.71, 190–194.10.1006/mgme.2000.3071Search in Google Scholar PubMed
Taupin, P. (2006). HuCNS-SC (StemCells). Curr. Opin. Mol. Ther.8, 156–163.Search in Google Scholar
Tian, Y., Sohar, I., Taylor, J.W., and Lobel, P. (2006). Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates. J. Biol. Chem.281, 6559–6572.10.1074/jbc.M507336200Search in Google Scholar PubMed
Tsai, B., Ye, Y., and Rapoport, T.A. (2002). Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell Biol.3, 246–255.10.1038/nrm780Search in Google Scholar
Tsiakas, K., Steinfeld, R., Storch, S., Ezaki, J., Lukacs, Z., Kominami, E., Kohlschutter, A., Ullrich, K., and Braulke, T. (2004). Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity. Glycobiology4, 1C–5C.10.1093/glycob/cwh054Search in Google Scholar
Uvebrant, P. and Hagberg, B. (1997). Neuronal ceroid lipofuscinoses in Scandinavia. Epidemiology and clinical pictures. Neuropediatrics28, 6–8.Search in Google Scholar
Vellodi, A. (2005). Lysosomal storage disorders. Br. J. Haematol.128, 413–431.10.1111/j.1365-2141.2004.05293.xSearch in Google Scholar
Vines, D. and Warburton, M.J. (1998). Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen. Biochim. Biophys. Acta1384, 233–242.10.1016/S0167-4838(98)00012-0Search in Google Scholar
Waldburg, N., Kahne, T., Reisenauer, A., Rocken, C., Welte, T., and Buhling, F. (2004). Clinical proteomics in lung diseases. Pathol. Res. Pract.200, 147–154.10.1016/j.prp.2004.02.006Search in Google Scholar
Walus, M., Kida, E., Wisniewski, K.E., and Golabek, A.A. (2005). Ser475, Glu272, Asp276, and Asp360 are involved in catalytic activity of human tripeptidyl-peptidase I. FEBS Lett.579, 1383–1388.10.1016/j.febslet.2005.01.035Search in Google Scholar
Wisniewski, K.E., Kaczmarski, A., Kida, E., Connell, F., Kaczmarski, W., Michalewski, M.P., Moroziewicz, D.N., and Zhong, N. (1999). Reevaluation of neuronal ceroid lipofuscinoses: atypical juvenile onset may be the result of CLN2 mutations. Mol. Genet. Metab.66, 248–252.10.1006/mgme.1999.2814Search in Google Scholar
Wisniewski, K.E., Kida, E., Golabek, A.A., Kaczmarski, W., Connell, F., and Zhong, N. (2001a). Neuronal ceroid lipofuscinosis: classification and diagnosis. Adv. Genet.45, 1–34.10.1016/S0065-2660(01)45002-4Search in Google Scholar
Wisniewski, K.E., Kida, E., Walus, M., Wujek, P., Kaczmarski, W., and Golabek, A.A. (2001b). Tripeptydyl-peptidase I in neuronal ceroid lipofuscinoses and other lysosomal storage disorders. Eur. J. Paediatr. Neurol.5, 73–79.10.1053/ejpn.2000.0439Search in Google Scholar PubMed
Wlodawer, A., Li, M., Gustchina, A., Oyama, H., Dunn, B.M., and Oda, K. (2003a). Structural and enzymatic properties of the sedolisin family of serine-carboxyl peptidases. Acta Biochim. Pol.50, 81–102.10.18388/abp.2003_3716Search in Google Scholar
Wlodawer, A., Durell, S.R., Li, M., Oyama, H., Oda, K. and Dunn, B.M. (2003b). A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases. BMC Struct. Biol.3, 8.Search in Google Scholar
Wujek, P., Kida, E., Walus, M., Wisniewski, K.E., and Golabek, A.A. (2004). N-Glycosylation is crucial for folding, trafficking, and stability of human tripeptidyl-peptidase I. J. Biol. Chem.279, 12827–12839.10.1074/jbc.M313173200Search in Google Scholar PubMed
Yoshida, M., Muneyuki, E., and Hisabori, T. (2001). ATP synthase-a marvelous rotary engine of the cell. Nat. Rev. Mol. Cell. Biol.2, 669–677.10.1038/35089509Search in Google Scholar PubMed
Zhong, N., Wisniewski, K.E., Hartikainen, J., Ju, W., Moroziewicz, D.N., McLendon, L., Sklower, Brooks, S.S., and Brown, W.T. (1998). Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis. Clin. Genet.54, 234–238.Search in Google Scholar
©2006 by Walter de Gruyter Berlin New York