The peptidases from fungi and viruses
-
Michael N.G. James
Abstract
Fungi and viruses encode a variety of peptidases having a plethora of functions. Many fungal peptidases are extracellular and are likely used to degrade proteins in their environment. Viral peptidases are processing enzymes, intimately involved in the virus infectious cycle. The viral RNA genome is translated by the host-cell machinery into a large polyprotein that is cleaved by the viral peptidases into mature capsid proteins, non-structural proteins and enzymes. I review the structure and catalytic mechanism of scytalidoglutamic peptidase isolated from the wood-destroying fungus Scytalidium lignicolum. This enzyme has a unique β-sandwich fold and a novel catalytic mechanism based on a glutamate, a glutamine and a nucleophilic water molecule. Hepatitis A virus (HAV) 3C peptidase was the first structure identified for a viral 3C enzyme that exhibited the three-dimensional fold of the chymotrypsin family of serine peptidases but had a cysteine sulfur atom instead of the serine oxygen as the nucleophile. The structure of HAV 3C was unusual in that the Asp residue expected as the third member of the catalytic triad did not interact with the general base His. The present structure is of a β-lactone-inhibited version of HAV 3C that has a restored catalytic triad.
References
Allaire, M., Chernaia, M.M., Malcolm, B.A., and James, M.N. (1994). Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases. Nature369, 72–76.10.1038/369072a0Search in Google Scholar PubMed
Andino, R., Rieckhof, G.E., Trono, D., and Baltimore, D. (1990). Substitutions in the protease (3Cpro) gene of poliovirus can suppress a mutation in the 5′ non-coding region. J. Virol.64, 607–612.10.1128/jvi.64.2.607-612.1990Search in Google Scholar PubMed PubMed Central
Bergmann, E.M. and James, M.N.G. (2000). The 3C proteinases of picornaviruses and other positive-sense, single-stranded RNA viruses. In: Handbook of Experimental Pharmacology, vol. 140, K. von der Helm, B. Korant and J.C. Cheronis, eds. (Heidelberg, Germany: Springer), pp. 117–143.10.1007/978-3-642-57092-6_7Search in Google Scholar
Bergmann, E.M., Mosimann, S.C., Chernaia, M.M., Malcolm, B.A., and James, M.N. (1997). The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition. J. Virol.71, 2436–2448.10.1128/jvi.71.3.2436-2448.1997Search in Google Scholar PubMed PubMed Central
Bergmann, E.M., Cherney, M.M., McKendrick, J., Frormann, S., Luo, C., Malcolm, B.A., Vederas, J.C., and James, M.N. (1999). Crystal structure of an inhibitor complex of the 3C proteinase from hepatitis A virus (HAV) and implications for the polyprotein processing in HAV. Virology267, 153–163.10.1006/viro.1999.9968Search in Google Scholar PubMed
Betzel, C., Pal, G.P., and Saenger, W. (1988). Three-dimensional structure of proteinase K at 0.15 nm resolution. Eur. J. Biochem.178, 155–171.10.1111/j.1432-1033.1988.tb14440.xSearch in Google Scholar PubMed
Birtley, J.R., Knox, S.R., Jaulent, A.M., Brick, P., Leatherbarrow, R.J., and Curry, S. (2005). Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity. J. Biol. Chem.280, 11520–11527.10.1074/jbc.M413254200Search in Google Scholar PubMed
Dragovich, P.S., Webber, S.E., Babine, R.E., Fuhrman, S.A., Patick, A.K., Matthews, D.A., et al. (1998). Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure-activity studies. J. Med. Chem.41, 2819–2834.Search in Google Scholar
Fujinaga, M., Cherney, M.M., Oyama, H., Oda, K., and James, M.N.G. (2004). The molecular structure and catalytic mechanism of a novel carboxyl peptidase from Scytalidium lignicolum. Proc. Natl. Acad. Sci. USA101, 3364–3369.10.1073/pnas.0400246101Search in Google Scholar PubMed PubMed Central
Gamarnik, A.V., and Andino, R. (2000). Interactions of viral protein 3CD and poly(rC) binding protein with the 5' untranslated region of the poliovirus genome. J. Virol.74, 2219–2226.10.1128/JVI.74.5.2219-2226.2000Search in Google Scholar
Gerber, K., Wimmer, E., and Paul, A.V. (2001). Biochemical and genetic studies of the initiation of human rhinovirus 2 RNA replication: purification and enzymatic analysis of the RNA-dependent RNA polymerase 3D(pol). J. Virol.75, 10969–10978.10.1128/JVI.75.22.10969-10978.2001Search in Google Scholar PubMed PubMed Central
James, M.N.G. (2004). Catalytic pathways of aspartic peptidases. In: Handbook of Proteolytic Enzymes, 2nd edition, A.J. Barrett, N.D. Rawlings, and J.F. Woessner, eds. (London, UK: Elsevier Ltd.), pp. 12–19.10.1016/B978-0-12-079611-3.50010-0Search in Google Scholar
James, M.N.G. and Sielecki, A.R. (1983). Structure and refinement of penicillopepsin at 1.8 Å resolution. J. Mol. Biol.163, 299–361.Search in Google Scholar
James, M.N.G., Sielecki, A.R., Salituro, F., Rich, D.H., and Hofmann, T. (1982). Conformational flexibility in the active sites of aspartyl proteinases revealed by a pepstatin fragment binding to penicillopepsin. Proc. Natl. Acad. Sci. USA79, 6137–6141.10.1073/pnas.79.20.6137Search in Google Scholar PubMed PubMed Central
James, M.N.G., Sielecki, A.R., Hayakawa, K., and Gelb, M.H. (1997). Crystallographic analysis of transition state mimics bound to penicillopepsin: difluorostatine- and difluorostatone-containing peptides. Biochemistry31, 3872–3886.Search in Google Scholar
Kataoka, Y., Takada, K., Oyama, H., Tsumani, M., James, M.N.G., and Oda, K. (2005). Catalytic residues and substrate specificity of scytalidoglutamic peptidase, the first member of the eqolisin family (G1) of peptidases. FEBS Lett.579, 2991–2994.10.1016/j.febslet.2005.04.050Search in Google Scholar PubMed
Lall, M.S., Karvellas, C., and Vederas, J.C. (1999). β-Lactones as a new class of cysteine proteinase inhibitors: inhibition of hepatitis A virus 3C proteinase by N-Cbz-serine β-lactone. Org. Lett.1, 803–806.10.1021/ol990148rSearch in Google Scholar PubMed
Lall, M.S., Ramtohul, Y.K., James, M.N., and Vederas, J.C. (2002). Serine and threonine β-lactones: a new class of hepatitis A virus 3C cysteine proteinase inhibitors. J. Org. Chem.67, 1536–1547.10.1021/jo0109016Search in Google Scholar PubMed
Lee, T.-W., Cherney, M.M., Huitema, C., Liu, J., James, K.E., Powers, J.C., Eltis, L.D., and James, M.N.G. (2005). Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like Aza-peptide epoxide. J. Mol. Biol.353, 1137–1151.10.1016/j.jmb.2005.09.004Search in Google Scholar PubMed PubMed Central
Mosimann, S.C., Cherney, M.M., Sia, S., Plotch, S., and James, M.N. (1997). Refined X-ray crystallographic structure of the poliovirus 3C gene product. J. Mol. Biol.273, 1032–1047.10.1006/jmbi.1997.1306Search in Google Scholar PubMed
Murao, S., Oda, K., and Matsushita, Y. (1972). New acid proteases from Scytalidium lignicolum M-133. Agric. Biol. Chem.37, 1417–1421.Search in Google Scholar
Oda, K. and Murao, S. (1991). Pepstatin-insensitive carboxyl proteinases. In: Structure and Function of the Aspartic Proteinases: Genetics, Structures, and Mechanisms, B.M. Dunn, ed. (New York, USA: Plenum Press), pp. 185–201.10.1007/978-1-4684-6012-4_23Search in Google Scholar PubMed
Rawlings, N.D., Tolle, D.P., and Barrett, A.J. (2004). MEROPS: the peptidase database. Nucleic Acids Res.32, D160–D164.10.1093/nar/gkh071Search in Google Scholar PubMed PubMed Central
Rossmann, M.G. (1972). The Molecular Replacement Method (New York, USA: Gordon and Breach).Search in Google Scholar
Wlodawer, A. and Erickson, J.W. (1993). Structure based inhibitors of HIV-1 protease. Annu. Rev. Biochem.62, 543–585.10.1146/annurev.bi.62.070193.002551Search in Google Scholar PubMed
Yang, Y., Rijnbrand, R., Watowich, S., and Lemon, S.M. (2004). Genetic evidence for an interaction between a picornaviral cis-acting RNA replication element and 3CD protein. J. Biol. Chem.279, 12659–12667.10.1074/jbc.M312992200Search in Google Scholar PubMed
Yin, J., Paul, A.V., Wimmer, E., and Rieder, E. (2003). Functional dissection of a poliovirus cis-acting replication element [PV-cre(2C)]: analysis of single- and dual-cre viral genomes and proteins that bind specifically to PV-cre RNA. J. Virol.77, 5152–5166.10.1128/JVI.77.9.5152-5166.2003Search in Google Scholar
Yin, J., Bergmann, E.M., Cherney, M.M., Lall, M.S., Jain, R.P., Vederas, J.C., and James, M.N.G. (2005). Dual modes of modification of hepatitis A virus 3C protease by a serine-derived β-lactone – selective crystallization and formation of a functional catalytic triad in the active site. J. Mol. Biol.354, 854–871.10.1016/j.jmb.2005.09.074Search in Google Scholar PubMed PubMed Central
©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Caspase-containing complexes in the regulation of cell death and inflammation
- Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death
- The peptidases from fungi and viruses
- C. elegans as a model system to study the function of the COG complex in animal development
- Functional responses of bone cells to thrombin
- Homologous substitution of ACE C-domain regions with N-domain sequences: effect on processing, shedding, and catalytic properties
- Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite
- Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata
- Single-cell resolution imaging of membrane-anchored hepatitis C virus NS3/4A protease activity
- Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS
- Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome
- Tripeptidyl-peptidase I in health and disease
- Molecular and functional analysis of new members of the wheat PR4 gene family
- C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity
- Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
- Heparin modulation of human plasma kallikrein on different substrates and inhibitors
- Adaptation of the behaviour of an aspartic proteinase inhibitor by relocation of a lysine residue by one helical turn
- Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in mice
Articles in the same Issue
- Caspase-containing complexes in the regulation of cell death and inflammation
- Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death
- The peptidases from fungi and viruses
- C. elegans as a model system to study the function of the COG complex in animal development
- Functional responses of bone cells to thrombin
- Homologous substitution of ACE C-domain regions with N-domain sequences: effect on processing, shedding, and catalytic properties
- Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite
- Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata
- Single-cell resolution imaging of membrane-anchored hepatitis C virus NS3/4A protease activity
- Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS
- Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome
- Tripeptidyl-peptidase I in health and disease
- Molecular and functional analysis of new members of the wheat PR4 gene family
- C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity
- Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
- Heparin modulation of human plasma kallikrein on different substrates and inhibitors
- Adaptation of the behaviour of an aspartic proteinase inhibitor by relocation of a lysine residue by one helical turn
- Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in mice