We have recently isolated an abundant cytosolic protein from human T-cells which specifically binds the immunosuppressive agent, FK-506. The FK-506-binding protein (FKBP) is a member of a novel class of proteins possessing peptidyl-prolyl cis-trans isomerase activity. These proteins are believed to play an important role in accelerating the rate at which proteins fold into their native conforma...

Reactive oxygen species have been implicated in the pathogenesis of atherosclerosis, hypertension, and restenosis, in part by promoting vascular smooth muscle cell (VSMC) growth. Many VSMC growth factors are secreted by VSMC and act in an autocrine manner. Here we demonstrate that cyclophilin A (CyPA), a member of the immunophilin family, is secreted by VSMCs in response to oxidative stress and...

Eukaryotic transcription is regulated predominantly by the post-translational modification of the participating components. One such modification is the cis-trans isomerization of peptidyl-prolyl bonds, which results in a conformational change in the protein involved. Enzymes that carry out this reaction include the yeast peptidyl-prolyl cis/trans isomerase Ess1 and its human counterpart Pin1, ...

Regulation of translating ribosomes is a major component of gene expression control network. In Escherichia coli, ribosome stalling by the C-terminal arrest sequence of SecM regulates the SecA-dependent secretion pathway. Previous studies reported many residues of SecM peptide and ribosome exit tunnel are critical for stalling. However, the underlying molecular mechanism is still not clear at t...

Rhomboid-family intramembrane proteases regulate important biological processes and have been associated with malaria, cancer, and Parkinson's disease. However, due to the lack of potent, selective, and pharmacologically compliant inhibitors, the wide therapeutic potential of rhomboids is currently untapped. Here, we bridge this gap by discovering that peptidyl α-ketoamides substituted at the k...

Analysis of the human repertoire of the FK506-binding protein family of peptidyl-prolyl cis/trans isomerases (FKBPs) has identified an expansion of genes that code for human FKBPs in the secretory pathway. There are distinct differences in tissue distribution and expression levels of each variant. We describe here the characterisation of human FKBP19 (Entrez Gene ID: FKBP11), an FK506-binding p...

The solid-phase Edman degradation procedure as proposed by Laursen [ 1] is ideally suited to the evaluation of peptidyl-resin products resulting from Merrifield solid-phase synthesis [2,3] of peptides. Incomplete deprotection and incomplete coupling reactions which occur during synthesis have been detected using quantitative Edman degradation [4,5]. However, extended sequencing experiments were...

The cyclophilins are a large family of proteins implicated in folding, transport and regulation of other proteins and are potential drug targets in cancer and in some viral and parasitic infections. The functionality of cyclophilins appears to depend on peptidyl-prolyl cis-trans isomerase (foldase) and/or molecular chaperone activities. In this study we assessed the peptidyl-prolyl isomerase an...

The dynamic combinatorial assembly of independent modules A and B through oxorhenium(V) coordination by a NS2+S motif in the presence of cyclophilin hCyp-18-an important peptidyl-prolyl isomerase-was investigated. Increasing glutathione (GSH) concentrations were used to dissociate [ARe(V)OB] complexes that displayed low affinity for hCyp-18. Conversely, coordinates that displayed submicromolar ...

The effect of antibiotics and other agents on-peptide bond synthesis by mammalian polyribosomes was determined by studying peptidyl-puromycin synthesis. Sparsomycin, anisomycin, cycloheximide, gougerotin, blasticidin S, and cryptopleurine inhibited the reaction. Sparsomycin and anisomytin inhibited the peptidyl-puromycin synthesis competitively with respect to puromycin. Arabinose analogs of pu...