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Tadashi Maruyama - One of the best experts on this subject based on the ideXlab platform.

  • fk506 binding protein from a thermophilic archaeon methanococcus thermolithotrophicus has chaperone like activity in vitro
    Biochemistry, 2000
    Co-Authors: Masahiro Furutani, Akira Ideno, Toshii Iida, Tadashi Maruyama
    Abstract:

    The in vitro protein folding activity of an FKBP (FK506 binding protein, abbreviated to MTFK) from a thermophilic archaeon, Methanococcus thermolithotrophicus, was investigated. MTFK exhibited FK506 sensitive PPIase (peptidyl prolyl cis−trans Isomerase) activity which accelerated the speed of ribonuclease T1 refolding, which is rate-limited by isomerization of two prolyl peptide bonds. In addition, MTFK suppressed the aggregation of folding intermediates and elevated the final yield of rhodanese refolding. We called this activity of MTFK the chaperone activity. The chaperone activity of MTFK was also inhibited by FK506. Alignment of the amino acid sequences of MTFK with human FKBP12 showed that MTFK has two insertion sequences, consisting of 13 and 44 amino acids, at the N- and C-termini, respectively [Furutani, M., Iida, T., Yamano, S., Kamino, K., and Maruyama, T. (1998) J. Bacteriol. 180, 388−394]. To study the relationship between chaperone and PPIase activities of MTFK, mutant MTFKs with deletions of...

  • biochemical and genetic characterization of an fk506 sensitive peptidyl prolyl cis trans Isomerase from a thermophilic archaeon methanococcus thermolithotrophicus
    Journal of Bacteriology, 1998
    Co-Authors: Masahiro Furutani, Toshii Iida, Shigeyuki Yamano, Kei Kamino, Tadashi Maruyama
    Abstract:

    A peptidyl prolyl Cis-Trans Isomerase (PPIase) was purified from a thermophilic methanogen, Methanococcus thermolithotrophicus. The PPIase activity was inhibited by FK506 but not by cyclosporine. The molecular mass of the purified enzyme was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 42 kDa by gel filtration. The enzyme was thermostable, with the half-lives of its activity at 90 and 100°C being 90 and 30 min, respectively. The catalytic efficiencies (kcat/Km) measured at 15°C for the peptidyl substrates, N-succinyl-Ala-Leu-Pro-Phe-p-nitroanilide and N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, were 0.35 and 0.20 μM−1 s−1, respectively, in chymotrypsin-coupled assays. The purified enzyme was sensitive to FK506 and therefore was called MTFK (M. thermolithotrophicus FK506-binding protein). The MTFK gene (462 bp) was cloned from an M. thermolithotrophicus genomic library. The comparison of the amino acid sequence of MTFK with those of other FK506-binding PPIases revealed that MTFK has a 13-amino-acid insertion in the N-terminal region that is unique to thermophilic archaea. The relationship between the thermostable nature of MTFK and its structure is discussed.

  • Gene for a cyclophilin-type peptidyl–prolyl cis–trans Isomerase from a halophilic archaeum, Halobacterium cutirubrum
    Gene, 1997
    Co-Authors: Toshii Iida, Masahiro Furutani, T Iwabuchi, Tadashi Maruyama
    Abstract:

    Abstract A gene encoding a cyclophilin (CyP)-type peptidyl–prolyl cis–trans Isomerase (PPIase) was cloned from a halophilic archaeum, Halobacterium cutirubrum DSM 669, and sequenced. Although amino-acid residues common to CyPs were conserved, an insertion that showed no homology to other CyPs was found in its N-terminal region. Sequence analysis revealed that the amino-acid sequence of this CyP was 40–45% identical to those of eukaryotes and Bacillus subtilis with high cyclosporin A sensitivity, but 27% identical to those of cyclosporin A-insensitive PPIases of Esherichia coli. The gene was also expressed in E. coli. The activity of purified recombinant CyP-type PPIase was stimulated by the addition of KCl, and was suppressed by cyclosporin A.

Masahiro Furutani - One of the best experts on this subject based on the ideXlab platform.

  • fk506 binding protein from a thermophilic archaeon methanococcus thermolithotrophicus has chaperone like activity in vitro
    Biochemistry, 2000
    Co-Authors: Masahiro Furutani, Akira Ideno, Toshii Iida, Tadashi Maruyama
    Abstract:

    The in vitro protein folding activity of an FKBP (FK506 binding protein, abbreviated to MTFK) from a thermophilic archaeon, Methanococcus thermolithotrophicus, was investigated. MTFK exhibited FK506 sensitive PPIase (peptidyl prolyl cis−trans Isomerase) activity which accelerated the speed of ribonuclease T1 refolding, which is rate-limited by isomerization of two prolyl peptide bonds. In addition, MTFK suppressed the aggregation of folding intermediates and elevated the final yield of rhodanese refolding. We called this activity of MTFK the chaperone activity. The chaperone activity of MTFK was also inhibited by FK506. Alignment of the amino acid sequences of MTFK with human FKBP12 showed that MTFK has two insertion sequences, consisting of 13 and 44 amino acids, at the N- and C-termini, respectively [Furutani, M., Iida, T., Yamano, S., Kamino, K., and Maruyama, T. (1998) J. Bacteriol. 180, 388−394]. To study the relationship between chaperone and PPIase activities of MTFK, mutant MTFKs with deletions of...

  • biochemical and genetic characterization of an fk506 sensitive peptidyl prolyl cis trans Isomerase from a thermophilic archaeon methanococcus thermolithotrophicus
    Journal of Bacteriology, 1998
    Co-Authors: Masahiro Furutani, Toshii Iida, Shigeyuki Yamano, Kei Kamino, Tadashi Maruyama
    Abstract:

    A peptidyl prolyl Cis-Trans Isomerase (PPIase) was purified from a thermophilic methanogen, Methanococcus thermolithotrophicus. The PPIase activity was inhibited by FK506 but not by cyclosporine. The molecular mass of the purified enzyme was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 42 kDa by gel filtration. The enzyme was thermostable, with the half-lives of its activity at 90 and 100°C being 90 and 30 min, respectively. The catalytic efficiencies (kcat/Km) measured at 15°C for the peptidyl substrates, N-succinyl-Ala-Leu-Pro-Phe-p-nitroanilide and N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, were 0.35 and 0.20 μM−1 s−1, respectively, in chymotrypsin-coupled assays. The purified enzyme was sensitive to FK506 and therefore was called MTFK (M. thermolithotrophicus FK506-binding protein). The MTFK gene (462 bp) was cloned from an M. thermolithotrophicus genomic library. The comparison of the amino acid sequence of MTFK with those of other FK506-binding PPIases revealed that MTFK has a 13-amino-acid insertion in the N-terminal region that is unique to thermophilic archaea. The relationship between the thermostable nature of MTFK and its structure is discussed.

  • Gene for a cyclophilin-type peptidyl-prolyl Cis-Trans Isomerase from a halophilic archaeum, Halobacterium cutirubrum.
    Gene, 1997
    Co-Authors: T Iida, Masahiro Furutani, T Iwabuchi, T. Maruyama
    Abstract:

    A gene encoding a cyclophilin (CyP)-type peptidyl prolyl Cis-Trans Isomerase (PPIase) was cloned from a halophilic archaeum, Halobacterium cutirubrum DSM 669, and sequenced. Although amino-acid residues common to CyPs were conserved, an insertion that showed no homology to other CyPs was found in its N-terminal region. Sequence analysis revealed that the amino-acid sequence of this CyP was 40-45% identical to those of eukaryotes and Bacillus subtilis with high cyclosporin A sensitivity, but 27% identical to those of cyclosporin A-insensitive PPIases of Escherichia coli. The gene was also expressed in E. coli. The activity of purified recombinant CyP-type PPIase was stimulated by the addition of KCl, and was suppressed by cyclosporin A.

  • Gene for a cyclophilin-type peptidyl–prolyl cis–trans Isomerase from a halophilic archaeum, Halobacterium cutirubrum
    Gene, 1997
    Co-Authors: Toshii Iida, Masahiro Furutani, T Iwabuchi, Tadashi Maruyama
    Abstract:

    Abstract A gene encoding a cyclophilin (CyP)-type peptidyl–prolyl cis–trans Isomerase (PPIase) was cloned from a halophilic archaeum, Halobacterium cutirubrum DSM 669, and sequenced. Although amino-acid residues common to CyPs were conserved, an insertion that showed no homology to other CyPs was found in its N-terminal region. Sequence analysis revealed that the amino-acid sequence of this CyP was 40–45% identical to those of eukaryotes and Bacillus subtilis with high cyclosporin A sensitivity, but 27% identical to those of cyclosporin A-insensitive PPIases of Esherichia coli. The gene was also expressed in E. coli. The activity of purified recombinant CyP-type PPIase was stimulated by the addition of KCl, and was suppressed by cyclosporin A.

Gunter Fischer - One of the best experts on this subject based on the ideXlab platform.

  • Aryl hetaryl ketones and thioketones as efficient inhibitors of peptidyl-prolyl Cis-Trans Isomerases.
    Chemistry & Biodiversity, 2012
    Co-Authors: Thomas Hediger, Gunter Fischer, Michael Schumann, Walter Frank, Manfred Braun
    Abstract:

    : A series of 18 differently substituted new aryl hetaryl ketones and thioketones were synthesized in four to six steps from commercial starting materials. The new ketones were evaluated as inhibitors of the peptidyl-prolyl Cis-Trans Isomerase hPin1 with K(i) values ranging in the one-digit micromolar to sub-micromolar numbers. A crystal structure revealed the non-planar arrangement of the aryl residues at the carbonyl compound and supports the hypothesis that the new compounds might mimic the transition state of the enzymatic conversion.

  • Peptide Bond cis/trans Isomerases: A Biocatalysis Perspective of Conformational Dynamics in Proteins
    Topics in Current Chemistry, 2011
    Co-Authors: Cordelia Schiene-fischer, Tobias Aumüller, Gunter Fischer
    Abstract:

    Peptide bond cis/trans Isomerases (PCTIases) catalyze an intrinsically slow rotational motion taking part in the conformational dynamics of a protein backbone in all of its folding states. In this way, PCTIases assist other proteins to shape their functionally active structure. They have been associated with viral, bacterial, and parasitic infection, signal transduction, cell differentiation, altered metabolic activity, apoptosis, and many other physiological and pathophysiological processes. The need to understand, characterize, and control biochemical steps which contribute to the folding of proteins is a problem being addressed in many laboratories today. This review discusses the biochemical basis that the peptidyl prolyl cis/trans Isomerase (PPIase) family of PCTIases uses for the control of bioactivity. Special emphasis is given to recent developments in the field of biocatalytic features of PPIases, the mechanism of catalysis, and enzyme inhibition.

  • Prolyl cis/trans Isomerase signalling pathways in cancer☆
    Current Opinion in Pharmacology, 2011
    Co-Authors: Martin Theuerkorn, Gunter Fischer, Cordelia Schiene-fischer
    Abstract:

    It is an emerging view that in many cases cell signalling relies on slow conformational interconversions of the backbone of key proteins as exemplified by the prolyl cis / trans isomerization, and that prolyl cis / trans Isomerases (PPIases), such as cyclophilins, FK506-binding proteins and the parvulin-like Pin1, serve to integrate temporally and spatially protein conformers with signalling events. The causal relationship between prolyl cis / trans isomerization catalysis, malignant transformation and tumour progression is not yet fully understood because of the pleiotropic biochemical effects characterizing these enzymes. However, recent studies on the role of cyclophilins and Pin1 indicate that PPIases utilize isomerization catalysis on client proteins under physiological and pathophysiological conditions. This knowledge could offer new cancer intervention strategies based on the development of isoenzyme-specific, tissue-specific and organelle-specific PPIase inhibitors.

  • reassessment of the role of fkbp38 in the rheb mtorc1 pathway
    FEBS Letters, 2009
    Co-Authors: Katharina Uhlenbrock, Matthias Weiwad, Reinhard Wetzker, Gunter Fischer, Alfred Wittinghofer, Ignacio Rubio
    Abstract:

    The small G-protein Rheb regulates cell growth via the mTORC1 complex by incompletely understood mechanisms. Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-Isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. We have conducted a comprehensive biochemical characterization of the Rheb/FKBP38 interaction. Using three different in vitro assays we did not detect an interaction between Rheb and FKBP38. Cell biological experiments illustrate that FKBP38 plays only a very minor, if any, role in mTORC1 activation. Our data document that FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation.

  • Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway
    FEBS Letters, 2009
    Co-Authors: Katharina Uhlenbrock, Matthias Weiwad, Reinhard Wetzker, Gunter Fischer, Alfred Wittinghofer, Ignacio Rubio
    Abstract:

    The small G-protein Rheb regulates cell growth via the mTORC1 complex by incompletely understood mechanisms. Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-Isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. We have conducted a comprehensive biochemical characterization of the Rheb/FKBP38 interaction. Using three different in vitro assays we did not detect an interaction between Rheb and FKBP38. Cell biological experiments illustrate that FKBP38 plays only a very minor, if any, role in mTORC1 activation. Our data document that FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation.

Toshii Iida - One of the best experts on this subject based on the ideXlab platform.

  • fk506 binding protein from a thermophilic archaeon methanococcus thermolithotrophicus has chaperone like activity in vitro
    Biochemistry, 2000
    Co-Authors: Masahiro Furutani, Akira Ideno, Toshii Iida, Tadashi Maruyama
    Abstract:

    The in vitro protein folding activity of an FKBP (FK506 binding protein, abbreviated to MTFK) from a thermophilic archaeon, Methanococcus thermolithotrophicus, was investigated. MTFK exhibited FK506 sensitive PPIase (peptidyl prolyl cis−trans Isomerase) activity which accelerated the speed of ribonuclease T1 refolding, which is rate-limited by isomerization of two prolyl peptide bonds. In addition, MTFK suppressed the aggregation of folding intermediates and elevated the final yield of rhodanese refolding. We called this activity of MTFK the chaperone activity. The chaperone activity of MTFK was also inhibited by FK506. Alignment of the amino acid sequences of MTFK with human FKBP12 showed that MTFK has two insertion sequences, consisting of 13 and 44 amino acids, at the N- and C-termini, respectively [Furutani, M., Iida, T., Yamano, S., Kamino, K., and Maruyama, T. (1998) J. Bacteriol. 180, 388−394]. To study the relationship between chaperone and PPIase activities of MTFK, mutant MTFKs with deletions of...

  • biochemical and genetic characterization of an fk506 sensitive peptidyl prolyl cis trans Isomerase from a thermophilic archaeon methanococcus thermolithotrophicus
    Journal of Bacteriology, 1998
    Co-Authors: Masahiro Furutani, Toshii Iida, Shigeyuki Yamano, Kei Kamino, Tadashi Maruyama
    Abstract:

    A peptidyl prolyl Cis-Trans Isomerase (PPIase) was purified from a thermophilic methanogen, Methanococcus thermolithotrophicus. The PPIase activity was inhibited by FK506 but not by cyclosporine. The molecular mass of the purified enzyme was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 42 kDa by gel filtration. The enzyme was thermostable, with the half-lives of its activity at 90 and 100°C being 90 and 30 min, respectively. The catalytic efficiencies (kcat/Km) measured at 15°C for the peptidyl substrates, N-succinyl-Ala-Leu-Pro-Phe-p-nitroanilide and N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, were 0.35 and 0.20 μM−1 s−1, respectively, in chymotrypsin-coupled assays. The purified enzyme was sensitive to FK506 and therefore was called MTFK (M. thermolithotrophicus FK506-binding protein). The MTFK gene (462 bp) was cloned from an M. thermolithotrophicus genomic library. The comparison of the amino acid sequence of MTFK with those of other FK506-binding PPIases revealed that MTFK has a 13-amino-acid insertion in the N-terminal region that is unique to thermophilic archaea. The relationship between the thermostable nature of MTFK and its structure is discussed.

  • Gene for a cyclophilin-type peptidyl–prolyl cis–trans Isomerase from a halophilic archaeum, Halobacterium cutirubrum
    Gene, 1997
    Co-Authors: Toshii Iida, Masahiro Furutani, T Iwabuchi, Tadashi Maruyama
    Abstract:

    Abstract A gene encoding a cyclophilin (CyP)-type peptidyl–prolyl cis–trans Isomerase (PPIase) was cloned from a halophilic archaeum, Halobacterium cutirubrum DSM 669, and sequenced. Although amino-acid residues common to CyPs were conserved, an insertion that showed no homology to other CyPs was found in its N-terminal region. Sequence analysis revealed that the amino-acid sequence of this CyP was 40–45% identical to those of eukaryotes and Bacillus subtilis with high cyclosporin A sensitivity, but 27% identical to those of cyclosporin A-insensitive PPIases of Esherichia coli. The gene was also expressed in E. coli. The activity of purified recombinant CyP-type PPIase was stimulated by the addition of KCl, and was suppressed by cyclosporin A.

Ignacio Rubio - One of the best experts on this subject based on the ideXlab platform.

  • reassessment of the role of fkbp38 in the rheb mtorc1 pathway
    FEBS Letters, 2009
    Co-Authors: Katharina Uhlenbrock, Matthias Weiwad, Reinhard Wetzker, Gunter Fischer, Alfred Wittinghofer, Ignacio Rubio
    Abstract:

    The small G-protein Rheb regulates cell growth via the mTORC1 complex by incompletely understood mechanisms. Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-Isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. We have conducted a comprehensive biochemical characterization of the Rheb/FKBP38 interaction. Using three different in vitro assays we did not detect an interaction between Rheb and FKBP38. Cell biological experiments illustrate that FKBP38 plays only a very minor, if any, role in mTORC1 activation. Our data document that FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation.

  • Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway
    FEBS Letters, 2009
    Co-Authors: Katharina Uhlenbrock, Matthias Weiwad, Reinhard Wetzker, Gunter Fischer, Alfred Wittinghofer, Ignacio Rubio
    Abstract:

    The small G-protein Rheb regulates cell growth via the mTORC1 complex by incompletely understood mechanisms. Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-Isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. We have conducted a comprehensive biochemical characterization of the Rheb/FKBP38 interaction. Using three different in vitro assays we did not detect an interaction between Rheb and FKBP38. Cell biological experiments illustrate that FKBP38 plays only a very minor, if any, role in mTORC1 activation. Our data document that FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation.