Analysis of structures and catalytic mechanisms of enzymes for development of novel functions
There has been no enzyme classification that has considered 3D-structures and catalytic mechanisms. Therefore, I will create a novel enzyme classification database, by analyzing and classifying enzyme functions, that is, catalytic mechanisms, based on the reaction types, each reaction step and structures of enzyme, cofactor, and substrate/product. Based on all the information, I am now developing a new enzyme classification, which can substitute for the conventional classification, Enzyme Commission Number.
More recently, I have been involved in the elucidation of biosynthetic mechanisms of secondary metabolites in filamentous fungi, based on my knowledge and experiences on enzyme reactions.
EzCatDB: A database of Enzyme Catalytic Mechanisms
(1) Nagano, Nozomi., Saito, Kazuki., Toriyama, Masaru., Imoto, Masakatsu. and Nakajima, Terumi. Mastoparan analog to elevate fertilization membrane of sea urchin eggs. In: "Peptide Chemistry 1992." Proceedings of the 2nd Japan Symposium on Peptide Chemistry. (eds. Yanaihara, N.) ESCOM (1992) 356-358
(2) Saito, K., Imoto, M., Nagano, N., Toriyama, M. and Nakajima, T. Such hydrophobic peptides as dansylated mastoparan can elevate the fertilization membrane of sea urchin eggs. (1995) Biochem. Biophys. Res. Commun. 215, 828-834.
(3) Nagano, Kozo. & Nagano, Nozomi. Transfer RNA docking pair model in the ribosomal pre- and post-translocational states. (1997) Nucleic Acids Res., 25, 1254-1264.
(4) Kozo Nagano & Nozomi Nagano (1997) Mechanism of decoding mRNA in Protein Biosynthesis (YAKUGAKU ZASSHI) 117, 749-763.
(5) David Gilbert, David Westhead, Nozomi Nagano & Janet Thornton (1999) Motif-based searching in TOPS protein topology databases. Bioinformatics, 15, 317-326.
(6) Nozomi Nagano, Motonori Ota & Ken Nishikawa (1999) Strong hydrophobic nature of cysteine residues in proteins. FEBS Lett. 458, 69-71.
(7) Nozomi Nagano, Gail Hutchinson & Janet Thornton (1999) Barrel structures in proteins - Automatic identification and classification including a sequence analysis of TIM barrels. Protein Sci., 8, 2072-2084.
(8) Nozomi Nagano, Craig Porter & Janet Thornton (2001) The (βα)8 glycosidases: Sequence and structure analyses suggest distant evolutionary relationships. Protein Eng., 14, 845-855.
(9) Nozomi Nagano, Christine Orengo & Janet Thornton (2002) One fold with many functions - The evolutionary relationships between TIM barrel families based on their sequences, structures and functions. J. Mol. Biol. 321, 741-765.
(10) Nozomi Nagano. (2005). EzCatDB: The Enzyme Catalytic-Mechanism Database. Nucleic Acids Research, Molecular Biology Database on-line compilation 2005, 613, Online Journal
(11) Nozomi Nagano. (2005). EzCatDB: The Enzyme Catalytic-Mechanism Database. Nucleic Acids Research, 33 (1) Database Issue, D407-D412, Online Journal
(12) Nozomi Nagano, Tamotsu Noguchi, Yutaka Akiyama (2007) "Systematic Comparison of Catalytic Mechanisms of Hydrolysis and Transfer Reactions Classified in the EzCatDB Database." PROTEINS: Structure, Function, and Bioinformatics. 66, 147-159.
(13) Chioko Nagao, Nozomi Nagano, Kenji Mizuguchi, (2010) "Relationships between functional subclasses and information contained in active-site and ligand-binding residues in diverse superfamilies." PROTEINS: Structure, Function, and Bioinformatics. 78, 2369-2384.
(14) Tsuyoshi Kato, Nozomi Nagano (2010) Metric Learning for Enzyme Active-Site Search. Bioinformatics, 26, 2698-2704.
(15) Motono C, Nakata J, Koike R, Shimizu K, Shirota M, Amemiya T, Tomii K, Nagano N, Sakaya N, Misoo K, Sato M, Kidera A, Hiroaki H, Shirai T, Kinoshita K, Noguchi T, Ota M (2011) SAHG, a comprehensive database of predicted structures of all human proteins. Nucleic Acids Research, 39 Database Issue, D487-D493.
(16) Tsuyoshi Kato, Nozomi Nagano (2011) Discriminative Structural Approaches for Enzyme Active-Site Prediction. BMC Bioinformatics, 12(suppl 1), S49.
(17) Umemura M, Koike H, Nagano N, Ishii T, Kawano J, Yamane N, Kozone I, Horimoto K, Shin-ya K, Asai K, Yu J, Bennett JW, Machida M (2013) "MIDDAS-M: motif-independent de novo detection of secondary metabolite gene clusters through the integration of genome sequencing and transcriptome data." PLoS One, 8, e84028
(18) Nagao C, Nagano N, Mizuguchi K (2014) "Prediction of detailed enzyme functions and identification of specificity determining residues by random forests." PLoS One, 9, e84623
(19) Myco Umemura, Nozomi Nagano, Hideaki Koike, Jin Kawano, Tomoko Ishii, Yuki Miyamura, Moto Kikuchi, Koichi Tamano, Jiujiang Yu, Kazuo Shin-ya, Masayuki Machida (2014) "Characterization of the biosynthetic gene cluster for the ribosomally synthesized cyclic peptide ustiloxin B in Aspergillus flavus." Fungal Genetics and Biology, 68, 23-30.
(20) Nagano N, Nakayama N, Ikeda K, Fukuie M, Yokota K, Doi T, Kato T, Tomii K. (2015) "EzCatDB: the enzyme reaction database, 2015 update." Nucleic Acids Res., 43, D453-D458.
(21) Takahiro Tsukui, Nozomi Nagano, Myco Umemura, Toshitaka Kumagai, Goro Terai, Masayuki Machida, Kiyoshi Asai (2015)
, "Ustiloxins, fungal cyclic peptides, are ribosomally synthesised in Ustilaginoidea virens." Bioinformatics, 31, 981-985.
(22) Gemma L. Holliday, Amos Bairoch, Pantelis G. Bagos, Arnaud Chatonnet, David J. Craik, Robert D. Flinn, Bernard Henrissat, David Landsman, Gerard Manning, Nozomi Nagano, Claire O'Donovan, Kim D. Pruitt, Neil D. Rawlings, Milton Saier, Ramanathan Sowdhamini, Michael Spedding, Narayanaswamy Srinivasan, Gert Vriend, Patricia C. Babbitt, Alex Bateman (2015), "Key challenges for the creation and maintenance of specialist protein resources." Proteins, 83, 1005-1013.
(23) Patricia C. Babbitt, Pantelis G. Bagos, Amos Bairoch, Alex Bateman, Arnaud Chatonnet, Mark Jinan Chen, David J. Craik, Robert D. Finn, David Gloriam, Daniel H. Haft, Bernard Henrissat, Gemma L. Holliday, Vignir Isberg, Quentin Kaas, David Landsman, Nicolas Lenfant, Gerard Manning, Nozomi Nagano, Narayanaswamy Srinivasan, Claire O'Donovan, Kim D. Pruitt, Ramanathan Sowdhamini, Neil D. Rawlings, Milton H. Saier, Jr., Joanna L. Sharman, Michael Spedding, Konstantinos D. Tsirigos, Ake Vastermark, Gerrit Vriend (2015), "Creating a Specialist Protein Resource Network: A meeting report for the Protein Bioinformatics and Community Resources Retreat." Database, 2015, bav063.
(24) Nagano N, Umemura M, Izumikawa M, Kawano J, Ishii T, Kikuchi M, Tomii K, Kumagai T, Yoshimi A, Machida M, Abe K, Shin-Ya K, Asai K (2016), "Class of cyclic ribosomal peptide synthetic genes in filamentous fungi." Fungal Genet Biol, 86, 58-70.
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