Revista Fitos
As proteases e seus inibidores estão amplamente distribuídos em todos os organismos vivos. São enzimas que desempenham funções crucias para a manutenção da vida e sua atividade é mantida sob estrito controle por mecanismos que incluem os inibidores e, se esta atividade não for controlada, pode acarretar doenças e até mesmo a morte do organismo. Os inibidores de ocorrência natural são peptídeos de tamanho variável e são classificados de acordo com o tipo de proteases que inibem. Os inibidores de serino-proteases são os mais importantes da natureza e também os mais expressos em plantas, e será o foco desta revisão. São classificados como inibidores canônicos, não-canônicos e Serpinas, de acordo com a estrutura e mecanismo de ação. As plantas expressam estes inibidores constitutivamente ou são induzidos por algum agente externo. Estes inibidores aumentam a resistência da planta a parasitos, insetos, larvas, microorganismos, pragas e patógenos em geral. São expressos geralmente nas sementes e grãos e levam a morte ou repelem o organismo invasor. Diversas pesquisas estão sendo conduzidas para purificar, caracterizar e avaliar o efeito de inibidores de serino-proteases em plantas no tratamento de diversas patologias humanas, inclusive alguns inibidores, como no caso dos inibidores de BBI de soja, já estão em estudos clínicos de fase II.
DOI
10.32712/2446-4775.2009.90
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BERG, T. Small-molecule inhibitors of protein-protein interactions. Current Opinion in Drug Discovery Development, v.11 p.666-74, 2008.
CHICHE, L.; HEITZ, A.; GELLY, J.C.; GRACY, J.; CHAU, P.T.T.; HA, P.T.; HERNANDEZ, J.F.; LE-NGUYEN, D. Squash inhibitors: From structural motifs to macrocyclic knottins. Current Protein Peptide Scence, v.5, p.341-349, 2004.
CHRISTELLER, J.T.; LAING, W. Plant serine proteinase inhibitors. Protein Peptide Letter, v.12, p.439-447, 2005.
CHRISTMANN, A.; WALTER, K.; WENTZEL, A.; KRÄTZNER, R.; KOLMAR, H. The cystine knot of a squash-type protease inhibitor as a structural scaffold for Escherichia coli cell surface display of conformationally constrained peptides. Protein Engineering, v.12, p.797-806, 1999.
CLEMENTE, A.; DOMONEY, C. Biological significance polymorphism in legume protease inhibitor the Bowman-Birk family. Current Protein Peptide Scence, v.7, p.201-216, 2006.
CRAIK, D.J.; DALY, N.L.; MULVENNA J.; PLAN, M.R.; TRABI, M. Discovery, structure and biological activities of the cyclotides. Current Protein Peptide Scence, v.5, p.297-315, 2004.
DELFÍN, J.; MARTÍNEZ, I.;ANTUCH, W.; MOREIRA, V.; GONZALÉZ, Y.; RODRÍGUEZ, R.; MÁRQUEZ, M.; SAROYÁN, A.; LARIONOVA, N.; DÍAZ, J.; PADRÓN, G.; CHÁVEZ, M. Purification, characterization and immobilization of proteinase inhibitors from Stichodactyla helianthus. Toxicon, v.34, p.1367-76, 1996.
DELL’AICA, I.; CANIATO, R.; BIGGIN, S.; GARBISA, S. Matrix proteases, green tea, and St. John’s wort: Biomedical research catches up with folk medicine. Clinical Chimical Acta, v.381, p.69-77, 2007.
FALCO, M.C.; SILVA-FILHO, M.C. Expression of soybean proteinase inhibitors in transgenic sugarcane plants: Effects on natural defense against Diatraea saccharalis. Plant Physiology Biochemistry, v.41, p.761-766, 2003.
FARADY, C.J.; EGEA, P.F.; SCHNEIDER, E.L.; DARRAGH, M.R.; CRAIK, C.S. Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition. Journal of Molecular Biology, v.380, p.351-360, 2008.
FEAR, G.; KOMARNYTSKY, S.; RASKIN, I. Proteases inhibitors and their peptidomimetic derivates as potential drugs. Pharmacology and Therapeutics, v.113, p.354-368, 2007.
GÖRANSSON, U.; SVANGAND, E.; CLAESON, P.; BOHLIN, L. Novel strategies for isolation and characterization of cyclotides: the discovery of bioactive macrocyclic plant polypeptides in the Violaceae. Current Protein Peptide Scence, v.5, p.317-29, 2004.
HEAL, W.P.; WICKRAMASINGHE, S.R.; TATE, E.W. Activity based chemical proteomics: profiling proteases as drug targets. Current Drug Discovery Technology, v.5, p.200-212, 2008.
KENNEDY, A.R. Chemopreventive agents: Protease inhibitors. Pharmacology and Therapeutics, v.78, p.167-209, 1998.
KROWARSCH, D.; CIERPICKI, T.; JELEN, F.; OTLEWSKI, J. Canonical protein inhibitors of serine proteases. Cellular Molecular Life Science, v.60, p.2427-2444, 2003.
KUESTER, D.; LIPPERT, H.; ROESSNER, A.; KRUEGER, S. The cathepsin family and their role in colorectal cancer. Pathology Research Practise, v.204, p.491-500, 2008.
LASKOWSKI, M.J.; KATO, I. Protein inhibitors of proteinases. Annual Review of Biochemistry, v.49, p.593-626, 1980.
LASKOWSKI, M.J.; QASIM, M.A. What can the structures of enzyme-inhibitor complexes tell us about the structures of enzyme substrate complexes? Biochimica et Biophysics Acta, v.1477, p.324-337, 2000.
LOSSO, J.N. The biochemical and functional food properties of the bowman-birk inhibitor. Critical Revision of Food Science Nutritional. v.48, n.1, p.94-118, 2008.
NEURATH, H. Proteolytic processing and physiological regulation. Trends Biochemistry Science, v.14, p.268-271, 1989.
OTLEWSKI J.; JELEN, F.; ZAKRZEWSKA, M.; OLESY, A. The many faces of protease-protein inhibitor Interaction. The EMBO Journal, v.24, p.1303-1310, 2005.
OTLEWSKI, J.; KROWARSCH, D. Squash inhibitor of serine proteinases. Acta Biochimica Polonica, v.43, p.431-444, 1996.
POWERS, J.C.; ASGIAN, J.L.; EKICI, O.; JAMES, K.E. Irreversible inhibitors of serine, cysteine and threonine proteases. Chemical Reviews, v.102, p. 4639-4750, 2002.
QI, R.F; SONG, Z.W.; CHI, C.W. Structural Features and Molecular Evolution of Bowman-Birk Protease Inhibitors and Their Potential Application. Acta Biochimica and Biophysics Sinica, v.37, p.283-292, 2005.
RAWLIINGS, N.D.; BARRET, A.J. Evolutionary families of peptidases. Biochememistry Journal, v.290, p.205-218, 1993.
RAWLINGS, N.D.; TOLLE, D.P.; BARRETT, A.J. Evolutionary families of peptidase inhibitors. Biochemistry Journal, v.378, p.705-716, 2004.
RAWLINGS, N.D.; MORTON, F.R. The MEROPS batch BLAST: A tool to detect peptidases and their non-peptidase homologues in a genome. Biochimie, v.90, p.243-259, 2008.
ROBERTS, T.H.; HEJGAARD, J. Serpins in plants and green algae. Function and Integrative Genomics, v.8, p.1-27, 2008.
SAMPATH, A., PADMANABHAN, R. Molecular targets for flavivirus drug discovery. Antiviral Research, v.81, p.124-132, 2008.
SCHECHTER I.; BERGER, A. Biochemistry and Biophysics Research Communications, v. 27, p.157-160, 1967.
SILVA-LOPEZ, R.E.; MORGADO-DÍAZ, J.A.; CHÁVEZ, M.A.; GIOVANNI-DE-SIMONE, S. (2007) Effects of serine protease inhibitors on viability and morphology of Leishmania (Leishmania) amazonensis promastigotes. Parasitology Research, v.101, p.1627-1635, 2007.
WILLIAMS, B.; DICKMAN, M. Plant programmed cell death: can’t live with it; can’t live without it. Molecular Plant Pathology, v.9, p.531-44, 2008.
WOODS, S.; FARRALL, A.; PROCKO, C.; WHITELAW, M.L. The bHLH/Per-Arnt-Sim transcription factor SIM2 regulates muscle transcript myomesin2 via a novel, non-canonical E-box sequence. Nucleic Acids Research, v.36, p.3716-27, 2008.
YANG, L.; TADA, Y.; YAMAMOTO, M.P.; ZHAO, H.; YOSHIKAWA, M.; TAKAIWA, F.A Transgenic rice seed accumulating an anti-hypertensive peptide reduces the blood pressure of spontaneously hypertensive rats. FEBS Letters, v.580, p.3315-3320, 2006.
YOSHIZAKI, L.; TRONCOSO, M.F.; LOPES, J.L.S.; HELLMAN, U.; BELTRAMINI, L.M.; WOLFENSTEIN-TODEL, C. Calliandra selloi Macbride trypsin inhibitor: Isolation, characterization, stability, spectroscopic analyses. Phytochemistry, v.68, p.2625-2634, 2007.
ZHANG, Y.; KOUZUMA, Y.; MIYAJI, T.; YONEKURA, M. Purification, characterization, and cDNA cloning of a Bowman-Birk type trypsin inhibitor from Apios americana Medikus tubers. Bioscience Biotechnology and Biochemistry, v.72, p.171-178, 2008.
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