Über Peptidyl‐Prolyl‐<i>cis/trans</i>‐Isomerasen und ihre Effektoren

Fischer, Gunter

doi:10.1002/ange.19941061404

Cited by 56 publications

(26 citation statements)

References 289 publications

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“…This investigation demonstrated that the prolyl isomerases were perfectly adapted enzymes according to their catalytic function. In some cases rate constants k cat /K M close to the diffusion limit of 2 ×10 8 M − 1 s − 1 were reported [74]. The standard spectrophotometric assay for PPIases, which uses isomer-specific proteases as helper enzymes, is simple and requires a minimum of effort for sample preparation and experimental equipment.…”

Section: The Cis/trans Prolyl Isomerase Activitymentioning

confidence: 98%

Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts

Göthel

Marahiel

1999

Cellular and Molecular Life Sciences (CMLS)

576

437

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Cyclosporine A therapy for prophylaxis against graft rejection revolutionized human organ transplantation. The immunosuppressant drugs cyclosporin A (CsA), FK506 and rapamycin block T-cell activation by interfering with the signal transduction pathway. The target proteins for CsA and FK506 were found to be cyclophilins and FK506-binding proteins, (FKBPs), respectively. They are unrelated in primary sequence, although both are peptidyl-prolyl cis-trans isomerases catalyzing the interconversion of peptidylprolyl imide bonds in peptide and protein substrates. However, the prolyl isomerase activity of these proteins is not essential for their immunosuppressive effects. Instead, the specific surfaces of the cyclophilin-CsA and FKBP-FK506 complexes mediate the immunosuppressive action. Moreover, the natural cellular functions of all but a few remain elusive. In some cases it could be demonstrated that prolyl isomerization is the rate-limiting step in protein folding in vitro, but many knockout mutants of single and multiple prolyl isomerases were viable with no detectable phenotype. Even though a direct requirement for in vivo protein folding could not be demonstrated, some important natural substrates of the prolyl isomerases are now known, and they demonstrate the great variety of prolyl isomerization functions in the living cell: (i) A human cyclophilin binds to the Gag polyprotein of the human immunodeficiency virus-1 (HIV-1) virion and was found to be essential for infection with HIV to occur, probably by removal of the virion coat. (ii) Together with heat shock protein (HSP) 90, a member of the chaperone family, high molecular weight cyclophilins and FKBPs bind and activate steroid receptors. This example also demonstrates that prolyl isomerases act together with other folding enzymes, for example the chaperones, and protein disulfide isomerases. (iii) An FKBP was found to act as a modulator of an intracellular calcium release channel. (iv) Along with the cyclophilins and FKBPs, a third class of prolyl isomerases exist, the parvulins. The human parvulin homologue Pin1 is a mitotic regulator essential for the G2/M transition of the eukaryotic cell cycle. These findings place proline isomerases at the intersection of protein folding, signal transduction, trafficking, assembly and cell cycle regulation.

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Section: The Cis/trans Prolyl Isomerase Activitymentioning

confidence: 98%

Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts

Göthel

Marahiel

1999

Cellular and Molecular Life Sciences (CMLS)

576

437

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“…[15] However, these methods suffer from some limitations. For example, the signal-tonoise ratio is low for the UV-resonance Raman spectroscopy method and signal overlapping is often encountered with the NMR spectroscopy method.…”

Section: Introductionmentioning

confidence: 99%

cis/trans Photoisomerization of Secondary Thiopeptide Bonds

Zhao

Micheau

Vargas

et al. 2004

Chemistry A European J

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The reversible cis/trans photoisomerization of secondary thiopeptide bonds has been systematically studied with UV-visible absorption, capillary electrophoresis, 1H NMR spectroscopy, and circular dichroism methods. It was found that the concentration of the cis conformers could be increased from less than 1 % in the thermal equilibrated solution to up to 20 % in the photostationary state. The rotational barriers of the thiopeptide bond and the pH dependence of the isomerization rates were also studied. The quantum yields of the trans-->cis and the cis-->trans processes were determined from photokinetic analysis.

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“…Peptidyl-prolyl cis/trans isomerases (PPIases, EC 5.2.1.8) are enzymes which catalyze the cisltrans isomerization of the peptidyl-prolyl bonds in oligopeptides and are thought to accelerate slow steps in protein folding and trafficking [1][2][3]. PPIases are ubiquitous and have been found in bacteria, fungi, mammals and plants.…”

Section: Introductionmentioning

confidence: 99%