Kyushu University Academic Staff Educational and Research Activities Database
Researcher information (To researchers) Need Help? How to update
Tadashi Ueda Last modified date:2018.07.04

Professor / Department of Medico-Pharmaceutical Scineces
Department of Pharmaceutical Health Care and Sciences
Faculty of Pharmaceutical Sciences

Undergraduate School
Other Organization
Administration Post

Laboratory of Protein Structure, Funcrion and Design, Graduate School of Pharmaceutical Sciences,
Kyushu University .
Academic Degree
Ph. D.
Country of degree conferring institution (Overseas)
Field of Specialization
Protein Engineering, Structural Biology
Total Priod of education and research career in the foreign country
Research Interests
  • Preparation of the antibodies tightly bound to P2X4 molecule, which is related to Allodynia.
    keyword : structure based drug design, P2X4 molecule, Allodynia
  • Improvement of enzymatic function for clinical application
    keyword : diabetes, stabilization, amino acid replacement
  • Study on denaturation or detorioration of proteins
    keyword : protein detorioration, aging, aggregation, conformational deseases、isomerization of amino acid residues in proteins
    2000.01Identification and characterization of structural or chemical alterations in proteins.
  • Antibody (or Fab) engineering
    keyword : antibody, mutation, protein engineering
    2002.04Protein engineering of a mouse antibody.
  • Structural biology of proteins
    keyword : proteins, NMR, X-ray crystallography, interaction
    2000.01Analysis of structure and function of lysozymes and proteins invovled in DNA replication in Escherichia coli..
Current and Past Project
  • Prof. Ueda in Kyushu University participates in protein 3000 project. We are preparing new proteins and determining their tertiary structures.
Academic Activities
1. Takatoshi Ohkuri, Tadashi Ueda, Taiji Imoto, Existence of Condensed Structures in Denatured Lysozyme and their Contributions to the Folding (ed. Tony R. Obalinsky) in Protein Folding: New Research, Nova Scieince Publisers. Inc., pp173-194, 2006.05.
2. Tadashi Ueda and Taiji Imoto, Identification of a core region and key residues in the refolding of reduced hen lysozyme (ed. by M. Gromiha and S. Selvaraj) in Recent Research Developments in Protein Folding, Stability and Design 2002, Reseach Signpost, Kerala, India,  pp.219-241, 2002.12.
1. Tadashi Ueda, Next-generation optimized biotherapeutics - A review and preclinical study., Biochim. Biophys. Acta. - Proteins and Proteomics, 2014.11.
2. Effect of Protein Structure of the Denatured State of the Formation of Amyloid Fibrils-Analysis Using Hen Egg White Lysozyme-.
1. Shohei Mine, Masahiro Watanabe, Saori Kamachi, Yoshito Abe, Tadashi Ueda, The structure of an archaeal β-glucosaminidase provides insight into glycoside hydrolase evolution., J. Biol. Chem., 10.1074/jbc.M116.766535., 292, 12, 4996-5006, 2017.01.
2. Yoshito Abe, Mitsuru Kubota, Shinta Takazaki, Yuji Ito, Hiromi Yamamoto, Dongchon Kang, Tadashi Ueda, Taiji Imoto, Effect on catalysis by replacement of catalytic residue from hen egg white lysozyme to Venerupis philippinarum lysozyme, Protein Science, 10.1002/pro.2966, 25, 9, 1637-1647, 2016.06.
3. Hitomi Nakamura, Takatoshi Ohkuri, Takanori So, Tadashi Ueda, Relationship between the magnitude of IgE production in mice and conformational stability of the house dust mite allergen, Der p 2., Biochimica et Biophysica Acta (BBA) - General Subjects, 10.1016/j.bbagen, in press, 2016.06.
4. Yoshito Abe, Naoki Fujisaki, Takanori Miyoshi, Noriko Watanabe, Tsutomu Katayama, Tadashi Ueda, Functional analysis of CedA based on its structure: residues important in binding of DNA and RNA polymerase and in the cell division regulation, The Journal of Biochemistry, 10.1093/jb/mvv096, 159, 2, 217-223, 2016.02.
5. Takahiro Aramaki, Yoshito Abe, Kaori Furutani, Tsutomu Katayama, Tadashi Ueda, Basic and aromatic residues in the C-terminal domain of PriC are involved in ssDNA and SSB binding., J. Biochem., 10.1093/jb/mvv014., 157, 6, 529-537, 2015.06.
6. Yoshito Abe, Takatoshi Ohkuri, Sachiko Yoshitomi, Tadashi Ueda, Role of the osmolyte taurine on the folding of a model protein, hen egg white lysozyme, under a crowding condition, AMINO ACIDS, 10.1007/s00726-015-1918-0, 47, 5, 909-915, 2015.05.
7. Tatsuhiro Igawa, Yoshito Abe, TSUDA MAKOTO, Kazuhide Inoue, Tadashi Ueda, Solution structure of the rat P2X4 receptor head domain involved in inhibitory metal binding, FEBS LETTERS, 10.1016/j.febslet.2015.01.034, 589, 6, 680-686, 2015.03.
8. Saki Fujiyama, Yoshito Abe, Junya Tani, Masashi Urabe, Kenji Sato, Takahiko Aramaki, Tsutomu Katayama, Tadashi Ueda, Structure and mechanism of the primosome protein DnaT-functional structures for homotrimerization, dissociation of ssDNA from the PriB.ssDNA complex, and formation of the DnaT.ssDNA complex, FEBS JOURNAL, 10.1111/febs.13080, 281, 23, 5356-5370, 2014.12.
9. Saki Fujiyama, Yoshito Abe, Taiichi Takenawa, Takahiko Aramaki, Seijiro Shioi, Tsutomu Katayama, Tadashi Ueda, Involvement of histidine in complex formation of PriB and single-stranded DNA, BBA-proteins and proteomics, 1844, 2, 299-307, 2014.02.
10. Takatoshi Ohkuri, Eri Murase, Sun Shu-Lan, Jun Sugitani, Tadashi Ueda, Characterization of deamidation at Asn138 in L-chain of recombinant humanized Fab expressed from Pichia pastoris, J.Biochem, 154, 4, 333-340, 2013.10.
11. Takahiko Aramaki, Yoshito Abe, Tsutomu Katayama, Tadashi Ueda, Solution structure of the N-terminal domain of a replication restart primosome factor, PriC, in Escherichia coli., Protein Science, 22, 9, 1279-1286, 2013.09.
12. Takahiko Aramaki, Yoshito Abe, Takatoshi Ohkuri, Tomonori Mishima, Shoji Yamashita, Tsutomu Katayama, Tadashi Ueda, Domain separation and characterization of PriC, a replication restart primosome factor in Escherichia coli. , Genes to Cells, 18, 9, 723-732, 2013.09.
13. Masato Abe, Yoshito Abe, Takaoshi Ohkuri, Tomonori Mishima, Akira Monji, Shigenobu Kanba, Tadashi Ueda, Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein., Protein Science, 22,4,467-474, 4, 467-474, 2013.04.
14. Tatsuhiro Igawa, Sadayuki Higashi, Yoshito Abe, Takatoshi Ohkuri, Hiroyuki Tanaka, satoshi morimoto, 山下 智大, TSUDA MAKOTO, Kazuhide Inoue, Tadashi Ueda, Preparation and characterization of a monoclonal antibody against the refolded and functional extracellular domain of rat P2X4 receptor, J. Biochem., 153, 3, 275-282, 2013.03.
15. Kameoka D, Ueda T, Imoto T., Effect of the Conformational Stability of the CH2 Domain on the Aggregation and Peptide Cleavage of a Humanized IgG., Appl Biochem Biotechnol., 164, 5, 642, 2011.07.
16. Ohkuri T, Nagatomo S, Oda K, So T, Imoto T, Ueda T, A Protein's conformational stability is an immunolgically dominant factor: Evidence that free-energy barriers for protein unfolding limit the immunolgenicity of foreign proteins, The Journal of Immunlogy, 185, 4199-4205, 2010.10, 蛋白質は立体構造を保持した状態でその機能を発揮する。蛋白質は往々にして、その安定性を高めることで有用性が上がることが知られている。一方、生体内で蛋白質抗原は、立体構造が壊れた状態で細胞内プロテアーゼにより分解され抗原性を発揮する。従って、免疫応答にも蛋白質の安定性が関与するということを示唆する知見は得られていた。本報告では、蛋白質抗原が免疫応答を引き起こす主要な要因の一つは、蛋白質抗原の構造安定性であることを世界で初めて実証した。この研究成果は,最近世界的に使用が広がっている抗体医薬品の機能を高めるためにアミノ酸配列を改変したとしても、不測の免疫応答を回避する方策を示唆したものである。この成果によって、今後、高機能化蛋白質医薬品の研究が一層進展することが期待される.
17. Tomonori Mishima, Takatoshi Ohkuri, Akira Monji, Takaaki Kanemaru, Yoshito Abe, Tadashi Ueda, Effect of His mutantions on the fibrillation of amyloidogenid Vλ6 protein Wil under acidic and physicological conditions, Biochemical and Biophysical Research Communication, 391, 1, 615, 2010.01.
18. Mishima T, Ohkuri T, Monji A, Kanemaru T, Abe Y, Ueda T, Residual Structures in the Acid-Unfolded States of Vlambda6 Proteins Affect Amyloid Fibrillation, J Mol Biol, 392(4):1033-43, 2009.10.
19. Ueda Y, Ohwada S, Abe Y, Shibata T, Iijima M, Yoshimitsu Y, Koshiba T, Nakata M, Ueda T, Kawabata SI., Factor G Utilizes a Carbohydrate-Binding Cleft That Is Conserved between Horseshoe Crab and Bacteria for the Recognition of {beta}-1,3-d-Glucan, J Immnol, 183(6):3810-8, 2009.09.
20. Keyamura K, Abe Y, Higashi M, Ueda T, Katayama T., DiaA dynamics are coupled with changes in initial origin complexes leading to helicase loading., J Biol Chem, 284(37):25038-50, 2009.09.
21. Makiko Nagata-Uchiyama, Masashi Yaguchi, Yugo Hirano and Tadashi Ueda, Expression and Purification of Uniformly 15N-Labeled Amyloid beta Peptide 1-40 in Escherichia coli, Protein & Peptide Letters, 14, 8, 788-792, 2007.09.
22. Goto T, Abe Y, Kakuta Y, Takeshita K, Imoto T, Ueda T, Crystal structure of Tapes japonica lysozyme with substrate analogue; Structural basis of the catalytic mechanism and manifestation of its chitinase activity accompany with quaternary structural change, Jounal of Biological Chemistry, 282、37、27459, 2007.09.
23. Kameoka D, Matsuzaki E, Ueda T, Imoto T, Effect of buffer species on the unfolding and the aggregation of humanized IgG, The Journal of Biochemistry, 142、3、383, 2007.09.
24. Yoshida Y, Ohkuri T, Takeda C, Kuroki R, Izuhara K, Imoto T, Ueda T, Analysis of internal motions of interleukin 13 variant associated with severe bronchial asthma using 15N relaxation measurements, Biochem. Biophys. Res. Commun., 358、1、292-297, 2007.06.
25. Abe Y, Jo T, Matsuda Y, Matsunaga C, Katayama T, Ueda T, Structure and function of DnaA N-terminal domains: Specific sites and mechanisms in inter-DnaA interaction and in DnaB helicase loading on Ori C, Jounal of Biological Chemistry, 282、24、17816-17827, 2007.06.
26. Fujii T, Ohkuri T, Onodera R, Ueda T, Stable supply of large amounts of human Fab from the inclusion bodies in E. coli., The Journal of Biochemistry, 141、5、699-707, 2007.05.
27. Mishima T, Ohkuri T, Monji A, Imoto T, Ueda T, A paticular hydrophobic cluster in the residual structure of reduced lysozyme drastically affects the amyloid fibrils formation, Biochem. Biophys. Res. Commun., 356, 3, 769-772, 2007.05.
28. Mishima T, Ohkuri T, Monji A, Imoto T, Ueda T, Amyloid formation in denatured single-mutant lysozyme where residual structures are modulated, Protein Science, 15, 10, 2448-2452, 2006.10.
29. Ohkuri T, Imoto T, Ueda T, Effect of W62G mutation of hen lysozyme on the folding in vivo, Biochem. Biophys Res. Commun., 10.1016/j.bbrc.2005.10.009, 338, 2, 820-824, 338, 2, 820-824, 2005.12.
30. Yoshida Y, Ohkuri T, Kino T, Ueda T and Imoto T, Elucidation of the relationship between enzyme activity and internal motion using a lysozyme stabilized by cavity-filling mutations, Cellular and Molecular Life Sciences, 10.1007/s00018-005-5053-z, 62, 9, 1047-1055, 62, 5, 1047-1055, 2005.05.
31. Ohkuri T, Shioi S, Imoto T, Ueda T, Effect of the structure of the denatured state of lysozyme on the aggregation reaction at the early stages of folding from the reduced form, J. Mol. Biol., 10.1016/j.jmb.2005.01.022, 347, 1, 159-168, 347、1、159-168, 2005.03.
32. Shioi S, Ose T, Maenaka K, Shiroishi M, Abe Y, Kohda D, Katayama T, Ueda T, Crystal structure of a biologically functional form of PriB from Escherichia coli reveals a potential single-stranded DNA-binding site, Biochem. Biophys. Res. Commun., 10.1016/j.bbrc.2004.11.104, 326, 4, 766-776, 326、4、766-776, 2005.01.
33. Ueno K, Ueda T, Sakai K, Abe Y, Hamasaki N, Okamoto M, Imoto T, Evidence for a novel racemization process of an asparaginyl residue in mouse lysozyme under physiological conditions, Cellular and Molecular Life Sciences, 10.1007/s00018-004-4412-5, 62, 2, 199-205, 62、2、199-205, 2005.01.
34. Wirmer J, Schlorb C, Klein-Seetharaman J, Hirano R, Ueda T, Imoto T, Schwalbe H, Modulation of compactness and long-range interactions of unfolded lysozyme by single point mutations, Angewandte Chemie-International Edition, 10.1002/anie.200460907, 43, 43, 5780-5785, 43、43、5780-5785, 2004.11.
35. Shioi S, Imoto T, Ueda T, Analysis of the early stage of the folding process of reduced lysozyme using all lysozyme variants containing a pair of cysteines, Biochemistry, 10.1021/bi036048h, 43, 18, 5488-5493, 43、18、5488-5493, 2004.05.
36. Yoshida Y, Obita T, Kokusho Y, Ohmura T, Katayama T, Ueda T, Imoto T., Identification of the region in Escherichia coli DnaA protein required for specific recognition of the DnaA box., Cell Mol Life Sci., 10.1007/s00018-003-3176-7, 60, 9, 1998-2008, 60, 9, 1998-2008, 2003.09.
37. Kameoka D, Ueda T, Imoto T., Method for the Detection of Asparagine Deamidation and Aspartate Isomerization of Proteins by MALDI/TOF-Mass Spectrometry Using Endoproteinase Asp-N., J Biochem., 134, 1, 129-135, 2003.07.
38. Obita T. Ueda T. Imoto T., Solution structure and activity of mouse lysozyme M., Cell. Mol. Life Sci., 10.1007/s000180300012, 60, 1, 176-184, 60, 1, 176-184, 2003.01.
39. Obita T. Iwura T. Su'etsugu M. Yoshida Y. Tanaka Y. Kayatama T. Ueda T. Imoto T., Determination of the secondary structure in solution of the Escherichia coli DnaA DNA-binding domain., Biochem. Biophys. Res. Commun., 10.1016/S0006-291X(02)02590-1, 299, 1, 42-48, 299, 1, 42-48, 2002.11.
40. Masumoto K. Ueda T. Nagata M. Yamada Y. Yoshida Y. Hashimoto Y. Imoto T., Effects of stereochemistry of sugars on protein stabilities., Protein Peptide Lett., 10.2174/0929866023408553, 9, 5, 435-439, 9, , 435-439, 2002.01.
41. Ohkuri T. Ueda T. Yoshida Y. Abe Y. Hamasaki N. Imoto T., A metal binding in the polypeptide chain improves the folding efficiency of a denatured and reduced protein., Biopolymers, 10.1002/bip.10153, 64, 2, 106-114, 642, 2, 106-114, 2002.02.
42. Nishida S. Fujimitsu K. Sekimizu K. Ohmura T. Ueda T. Katayama T., A nucleotide switch in the E. coli DnaA protein initiates chromosomal replication: Evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo., J. Biol. Chem., 10.1074/jbc.M108303200, 277, 17, 14986-14995, 277, 17, 14986-14995, 2002.02.
43. Klein-Seetharaman J, Oikawa M, Grimshaw S B, Wirmer J, Durchardt E, Ueda T.他4名, Long-range interactions within a nonnative protein., Science, 10.1126/science.1067680, 295, 5560, 1719-1722, 295, 5560, 1719-1722, 2002.03.
44. Ohkuri T. Ueda T. Tsurumaru M. Imoto T., Evidence for an initiation site for hen lysozyme folding from reduced form using its dissected peptide fragments., Protein Eng., 10.1093/protein/14.11.829, 14, 11, 829-833, 14, , 829-833, 2001.01.
45. Tsujihata Y. So T. Hashimoto Y. Ueda T. Imoto T., A single amino acid substitution in a self protein is sufficient to trigger autoantibody response., Mol. Immunol., 10.1016/S0161-5890(01)00068-2, 38, 5, 375-381, 38, , 375-381, 2001.01.
46. Ueda T. Nagata M. Imoto T., Aggregation and chemical reaction in hen lysozyme caused by heating at pH 6 are depressed by osmolytes, sucrose and trehalose., J. Biochem., 130, 4, 491-496, 130, ,491-496, 2001.01.
47. Ohmura T. Ueda T. Ootsuka K. Saito M. Imoto T., Stabilization of hen egg white lysozyme by a cavity-filling mutation., Protein Sci., 10.1110/ps.37401, 10, 2, 313-320, 10, 9, 313-320, 2001.09.
48. Ueda T. Masumoto K. Ishibashi R. So T. Imoto T., Remarkable thermal stability of doubly intramolecularly cross-linked hen lysozyme., Protein Eng., 10.1093/protein/13.3.193, 13, 3, 193-196, 13, , 193-196, 2000.01.
49. Tsujihata Y. So T. Chijiiwa Y. Hashimoto Y. Hirata M. Ueda T. Imoto T., Mutant mouse lysozyme carrying a minimal T cell epitope of hen egg lysozyme evokes high autoantibody, J. Immunol., 165, 7, 3606-3611, 165, 3, 606-3611, 2000.01.
50. Mine S. Ueda T. Hashimoto Y. Imoto T., Analysis of the internal motion of free and ligand-bound human lysozyme by use of N-15 NMR relaxation measurement: A comparison with those of hen lysozyme., Protein Sci., 9, 9, 1669-1684, 9, 9,1669-1684, 2000.09.
51. Mine S. Ueda T. Hashimoto Y. Tanaka Y. Imoto T., High-level expression of uniformly 15N-labeled hen lysozyme in Pichia pastoris and identification of the site in hen lysozyme where phosphate ion binds using NMR measurements., FEBS Letters, 10.1016/S0014-5793(99)00332-4, 448, 1, 33-37, 488, 1, 33-37, 1999.01.
52. So T. Ito HO. Hirata M. Ueda T. Imoto T., Extended blood half-life of monomethoxypolyethylene glycol-conjugated hen lysozyme is a key parameter controlling immunological tolerogenicity., Cell. Mol. Life Sci., 10.1007/s000180050365, 55, 8-9, 1187-1194, 55, , 1187-1194, 1999.01.
53. Mine S, Tate S, Ueda T, Kainosho M, Imoto T, Analysis of the relationship between enzyme activity and its internal motion using nuclear magnetic resonance:15N relaxation studies of wild-type and mutant lysozyme, Journal of Molecular Biology, 10.1006/jmbi.1999.2572, 286, 5, 1547-1565, 285、5、1547-1565, 1999.02.
54. Maeda Y. Ueda T. Imoto T., Effective renaturation of Met-1 lysozyme expressed in Escherichia coli as inclusion bodies., Protein and Peptide Letters, 5, 2, 67-74, 5, , 67-74, 1998.01.
55. Kawamura S. Abe Y. Ueda T. Masumoto K. Imoto T. Yamasaki N. Kimura M., Investigation of the structural basis for thermostability of DNA-binding protein HU from Bacillus stearothermophilus, Journal of Biological Chemistry, 10.1074/jbc.273.32.19982, 273, 32, 19982-19987, 273, , 19982-19987, 1998.01.
1. Tadashi Ueda, The effect of long-range interactions in the denatured state of a protein on the amyloid formations., Institue for Protein Research Seminar JSPS Japan Hungary Joint Seminar " Mechanism and regulation of aberrant protein aggregation", 2014.11.
2. Reina Fujita, 三次 百合香, Kenji Hamase, Takashi Saitoh, Fumina Ohsaka, Katsumi Maenaka, Mitsunori Shiroishi, Yoshito Abe, Tadashi Ueda, ANALYSIS OF ISOMERIZATION AT ASN127 IN MOUSE LYSOYME AT pH 7 WITHOUT DEAMIDATION, The 2nd International Conference of D-Amino Acid Research , 2014.09.
3. 荒牧峻彦, 阿部 義人, 大栗誉敏, 三島朋徳, 古谷佳織, 山下 昭二, 片山 勉, 植田 正, Domain separation and characterization of PriC, a replication restart primosome factor in Escherichia coli., Protein Society 2013 symposium, 2013.07.
4. High expression of human interleukin-13 receptor alpha 2 chain using Pichia pastoris.
5. Induction of antigen specific immunological tolerance using sugar mofidication or polymerization of antigen.
6. Tertiary structure of PriB involved in the formation of primosome complex in E. coli and its interaction with DNA.
7. Effect of staility of antigen protein on antibody production.
8. Evidence for the relation between enzymatic activity and internal motions using hen lysozyme stabilized by cavity filling mutations..
9. X-ray crystal structure of heat shock protein Q (Hsp Q) from Escherichia coli.