Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Keitaro Suyama Last modified date:2019.06.11

Assistant Professor / Laboratory of Molecular Biochamistry / Division for Experimental Natural Science / Faculty of Arts and Science

1. Xiaohui Liu, Hiroki Sakai, Mitsuhiro Nishigori, Keitaro Suyama, Tasuku Nawaji, Shin Ikeda, Makoto Nishigouchi, Hiroyuki Okada, Ayami Matsushima, Takeru Nose, Miki Shimohigashi, Yasuyuki Shimohigashi , Receptor-binding Affinities of Bisphenol A and Its Next-generation Analogs for Human Nuclear Receptors, Toxicology and Applied Pharmacology,, in press, 2019.06, An endocrine-disrupting chemical Bisphenol A (BPA) binds specifically to a nuclear receptor (NR) named ERRγ. Although the importance of receptor-binding evaluation for human NRs is often stressed, the binding characteristics of so-called next-generation (NextGen) bisphenol compounds are still poorly understood. The ultimate objective of this investigation was to evaluate BPA and its NextGen analogs for their abilities to bind to 21 human NRs, the greatest members of NRs for which tritium-labeled specific ligands were available. After establishing the detailed assay conditions for each NR, the receptor binding affinities of total 11 bisphenols were evaluated in competitive binding assays. The results clearly revealed that BPA and the NextGen bisphenols of BPAF, BPAP, BPB, BPC, BPE, and BPZ were highly potent against one or more of NRs such as CAR, ERα, ERβ, ERRγ, and GR, with IC50 values of 3.3–73 nM. These bisphenols were suggested strongly to be disruptive to these NRs. BPM and BPP also appeared to be disruptive, but less potently. BPF exhibited only weak effects and only against estrogen-related NRs. Surprisingly, most doubtful bisphenol BPS was supposed not to be disruptive. The NRs to which BPA and NextGen bisphenols did not bind were RARα, RARβ, RARγ, and VDR. PPARγ, RORα, RORβ, RORγ, RXRα, RXRβ, and RXRγ, exhibited very weak interaction with these bisphenols. The ten remaining NRs, namely, ERRγ, ERβ, ERα, CAR, GR, PXR, PR, AR, LXRβ, and LXRα, showed distinctly strong binding to some bisphenols in this order, being likely to have consequential endocrine-disruption effects..
2. Hitoshi Kesamaru, Keitaro Suyama, Takeru Nose*, Importance of Receptor Conformations in Docking Calculation-Based Risk Assessment for Endocrine Disruptors against Estrogen Receptor α, ACS Omega,, 4, 6620-6629, 2019.04, Employment of appropriate receptor conformations as templates is essential for appropriate identification of the latent receptor binding ability of chemicals using in silico docking calculations. In this study, we performed docking calculations using a number of agonist- and antagonist-bound conformations of 83 estrogen receptor (ER) α-ligand-binding domains as templates to clarify the type of receptor conformations required for reasonable identification of endocrine disruptors. Our results showed that 17β-estradiol and diethylstilbestrol (ERα agonists) bound preferentially to the agonist conformations, whereas 4-hydroxytamoxifen and raloxifene (ERα antagonists) bound selectively to the antagonist conformations. We also observed that bisphenol A analogues, which are partial agonists, bound more moderately and preferentially to the agonist conformations as compared with the antagonist conformations. Additionally, the docking calculations were able to estimate biological agonist or antagonist activity of chemicals based on the receptor conformation selectivity. Furthermore, structural analyses of the ligand-binding domains and docking calculation utilizing C-terminal-truncated receptors indicated that the C-terminal regions of these domains were capable of discriminating agonists from nonagonists. These results suggest that both agonist- and antagonist-binding conformations of receptors are necessary to predict the binding affinity and biological activity of chemicals for docking calculation-based risk assessment. Furthermore, this in silico method can be beneficial for drug discovery because it is useful for rapid searching of ligands for receptors and preventing the side effects caused by unfavorable receptor binding..
3. Keitaro Suyama, Daiki Tatsubo, Suguru Taniguchi, Iori Maeda, Takeru Nose, Development of Self-assembling Short Elastin-derived Peptide Analogs: Linear and Nonlinear (FPGVG)n Analogs, Peptide Science 2018, 117-117, 2018, 117., 2019.03, The elastin-derived peptide analog, (FPGVG)n, demonstrates temperature-dependent self-association (coacervation) property. In this study, we revealed that simple dimerization and cyclization of (FPGVG)n analogs induced strong coacervation ability compared to the ability of monomeric linear (FPGVG)5..
4. Keitaro Suyama, Daiki Tatsubo, Wataru Iwasaki, Masaya Miyazaki, Yuhei Kiyota, Ichiro Takahashi, Iori Maeda, Takeru Nose, Enhancement of self-aggregation properties of linear elastin-derived short peptides by simple cyclization
strong self-aggregation properties of cyclo[FPGVG]n, consisting only of natural amino acids, Biomacromolecules, 10.1021/acs.biomac.8b00353, 19, 8, 3201-3211, 2018.06, Elastin-like peptides (ELP) consist of distinctive repetitive sequences, such as (VPGVG)n, exhibit temperature-dependent reversible self-assembly (coacervation), and have been considered to be useful for the development of thermo-responsive materials. Further fundamental studies evaluating coacervative properties of novel nonlinear ELPs could present design concepts for new thermo-responsive materials. In this study, we prepared novel ELPs, cyclic (FPGVG)n (cyclo[FPGVG]n, n = 1-5), and analyzed its self-assembly properties and structural characteristics. Cyclo[FPGVG]n (n = 3-5) demonstrated stronger coacervation capacity than the corresponding linear peptides. The coacervate of cyclo[FPGVG]5 was able to retain water-soluble dye molecules at 40°C, which implied that cyclo[FPGVG]5 could be employed as a base material of DDS (Drug Delivery System) matrices and other biomaterials. The results of molecular dynamics simulations and circular dichroism measurements suggested that a certain chain length was required for cyclo[FPGVG]n to demonstrate alterations in molecular structure that were critical to the exhibition of coacervation..
5. Daiki Tatsubo, Keitaro Suyama, Masaya Miyazaki, Iori Maeda, and Takeru Nose, Stepwise Mechanism of Temperature-Dependent Coacervation of the Elastin-like Peptide Analogue Dimer, (C(WPGVG)3)2, Biochemistry, 10.1021/acs.biochem.7b01144, 57, 10, 1582-1590, 2018.06, Elastin-like peptides (ELPs) are distinct, repetitive, hydrophobic sequences, such as (VPGVG)n, that exhibit coacervation, the property of reversible, temperature-dependent self-association and dissociation. ELPs can be found in elastin and have been developed as new scaffold biomaterials. However, the detailed relationship between their amino acid sequences and coacervation properties remains obscure because of the structural flexibility of ELPs. In this study, we synthesized a novel, dimeric ELP analogue (H-C(WPGVG)3-NH2)2, henceforth abbreviated (CW3)2, and analyzed its self-assembly properties and structural factors as indicators of coacervation. Turbidity measurements showed that (CW3)2 demonstrated coacervation at a concentration much lower than that of its monomeric form and another ELP. In addition, the coacervate held water-soluble dye molecules. Thus, potent and distinct coacervation was obtained with a remarkably short sequence of (CW3)2. Furthermore, fluorescence microscopy, dynamic light scattering, and optical microscopy revealed that the coacervation of (CW3)2 was a stepwise process. The structural factors of (CW3)2 were analyzed by molecular dynamics simulations and circular dichroism spectroscopy. These measurements indicated that helical structures primarily consisting of proline and glycine became more disordered at high temperatures with concurrent, significant exposure of their hydrophobic surfaces. This extreme change in the hydrophobic surface contributes to the potent coacervation observed for (CW3)2. These results provide important insights into more efficient applications of ELPs and their analogues, as well as the coacervation mechanisms of ELP and elastin..
6. Hujun Li, Asako Inoue, Suguru Taniguchi, Tomohiko Yukutake, Keitaro Suyama, Takeru Nose, Iori Maeda, Multifunctional biological activities of water extract of housefly larvae (Musca domestica), PharmaNutrition, 10.1016/j.phanu.2017.09.001, 5, 4, 119-126, 2017.12, Many types of insects have been used as foods and protein sources. In this study, we investigated the usefulness of housefly larvae (Musca domestica) based on their amino acid composition and multifunctional biological activities. First, the utility of the amino acid composition of housefly larvae was evaluated by amino acid analysis. Notably, the housefly larvae contained sufficient amounts of all essential amino acids, and the amino acid composition was similar to that of hen eggs. Second, we prepared housefly larvae water extract (HLWE) using the decoction method and explored the biological activities of the extract for potential application of the extract as a functional food. HLWE showed significant antioxidant activity (75.4% at 5.00 mg/mL), angiotensin-I-converting enzyme (ACE) inhibitory activity (half-maximal inhibitory concentration [IC
] = 0.430 mg/mL), and dipeptidyl peptidase-IV (DPP-IV) inhibitory activity ([IC
] = 3.52 mg/mL). We found that the low-molecular-weight constituents (<6 kDa) in HLWE contributed to antioxidant and ACE-inhibitory activities, whereas the high-molecular-weight constituents (>6 kDa) contributed to DPP-IV inhibition. Our results suggested that housefly larvae may provide a useful source of multifunctional protein..
7. Keitaro Suyama, Daiki Tatsubo, Hitoshi Kesamaru, Iori Maeda, Takeru Nose, Coacervation Property and Structural Analysis of Cyclic Analogs of Elastin-derived Peptide (FPGVG)n, Peptide Science 2016, 101-102, 2017.03, The elastin-derived peptide analog, (FPGVG)5, demonstrates a temperature- dependent self-association (coacervation) property. In this study, we prepared cyclic (FPGVG)n (n=1-5) analogs and investigated their coacervation and structural properties to assess their potential for use as a biomaterial. We found that the cyclic (FPGVG)n (n=3-5) analogs exhibited high coacervation ability. The results from the molecular dynamics simulation suggest that turn structures were important for coacervation of elastin-derived cyclic peptide analogs..
8. Keitaro Suyama, Hitoshi Kesamaru, Daiki Tatsubo, Takeru Nose, Coacervation Properties and Structural Analysis of Aminobenzoyl-labeled Fluorescent Elastin-derived Peptides, Peptide Science 2015, 293-294, 2016.03, The elastin-derived peptide analog, (FPGVG)5, demonstrates a temperature- dependent self-association (coacervation) property. In this study, we prepared fluorescent-labeled (FPGVG)5 analogs, and evaluated their coacervation and fluorescent properties in order to assess their potential for use as a base material for fluorescent thermometers. We found that the fluorescent-labeled (FPGVG)5 analogs exhibited high coacervation ability. Results from the molecular dynamics calculation suggest that the fluorescent group is exposed on the surface of the molecule..
9. Daiki Tatsubo, Keitaro Suyama, Takeru Nose, Fluorescence Analysis Using a Molecular Probe 1,8-ANS for Elucidation of the Molecular Mechanisms Underlying Coacervation of a Tryptophan-containing Elastin derived Dimeric Peptide, Peptide Science 2015, 95-96, 2016.03, A tryptophan-containing elastin-derived dimeric peptide (C(WPGVG)3)2 shows potent self-assembly activity. To elucidate the underlying coacervation mechanisms, we measured the fluorescence of (C(WPGVG)3)2 by using 1,8-ANS as a fluorescent probe. The results revealed that the peptide forms microaggregates at temperature and concentration lower than those at which visible coacervation occurs. These findings suggest that microaggregate formation is unrelated to the maturation of the coacervate drop, which is temperature-dependent..
10. Keitaro Suyama, Suguru Taniguchi, Daiki Tatsubo, Iori Maeda, Takeru Nose, Dimerization effects on coacervation property of an elastin-derived synthetic peptide (FPGVG)5, Journal of Peptide Science, 10.1002/psc.2876, in press, 2016.03, A series of elastin-derived peptide (Phe-Pro-Gly-Val-Gly)5 dimers possessing high coacervation potential were synthesized. The new dimeric peptides showed significantly high coacervation ability compared to known elastin-derived peptide analogs. The molecular dynamics calculation results reveal that the dimeric peptides contain characteristic sheet-turnsheet motif involving a type II β-turn-like structure and form globular conformation..
11. Kanako Nishio, Hirokazu Nishimura, Keitaro Suyama, Takeru Nose, Yasuyuki Shimohigashi, Halogenated Phe-containing endomorphin-2 analogs with mixed agonist and antagonist activities, Peptide Science 2012, in press, 2013.03.
12. Yumi Kramitsu, Hirokazu Nishimura, Ryo Nakamura, Keitaro Suyama, Kazuhiro Matsumoto, Takeru Nose, Yasuyuki Shimohigashi, High-precision binding assay procedure of tachykinin receptor NK-1 for highly potent substance P analogs, Peptide Science 2012, in press, 2013.03.
13. Ryo Nakamura, Hirokazu Nishimura, Keitaro Suyama, Takeru Nose, Yasuyuki Shimohigashi, The Effect of Halogenation of Phe-Phenyl Group of Two Consecutive Phe Residues Present in Neuropeptide Substance P on Its Specific Receptor Interaction, Peptide Science 2011, 157-158, 2012.03.
14. Kanako Nishio, Hirokazu Nishimura, Keitaro Suyama, Yoshinori Abe, Takeru Nose, Ayami Matsushima, Yasuyuki Shimohigashi, Effects of the Halogenation of Phe-Phenyl Group of Two Consecutive Residues in Endomorphin-2 on the Interaction with the μ-Opioid Receptors, Peptide Science 2011, 171-172, 2012.03.
15. Keitaro Suyama, Kazuhiro Matsumoto, Tsutomu Katsuki, Asymmetric Lewis Acid Catalysis of Aluminum(salalen) Complexes: Friedel-Crafts Reaction of Indole, Heterocycles, 10.3987/COM-08-S(F)93, 77, 817-824, 2009.02.
16. Keitaro Suyama, Yoshifumi Sakai, Kazuhiro Matsumoto, Tsutomu Katsuki, Highly Enantioselective Hydrophosphonylation of Aldehydes: Base-Enhanced Aluminum-salalen Catalysis, Angewante Chemie, International Edition, 10.1002/anie.200905158, 49, 797-799, 2010.01.