908 results match your criteria isomerization proline

Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.

Biomedicines 2021 Mar 31;9(4). Epub 2021 Mar 31.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Peptidyl-prolyl isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. Read More

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Structure analysis suggests Ess1 isomerizes the carboxy-terminal domain of RNA polymerase II via a bivalent anchoring mechanism.

Commun Biol 2021 Mar 25;4(1):398. Epub 2021 Mar 25.

Department of Biochemistry and Molecular Biology, SUNY-Upstate Medical University, Syracuse, NY, USA.

Accurate gene transcription in eukaryotes depends on isomerization of serine-proline bonds within the carboxy-terminal domain (CTD) of RNA polymerase II. Isomerization is part of the "CTD code" that regulates recruitment of proteins required for transcription and co-transcriptional RNA processing. Saccharomyces cerevisiae Ess1 and its human ortholog, Pin1, are prolyl isomerases that engage the long heptad repeat (YSPTSPS) of the CTD by an unknown mechanism. Read More

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Protein yoga: Conformational versatility of the Hemolysin II C-terminal domain detailed by NMR structures for multiple states.

Protein Sci 2021 May 30;30(5):990-1005. Epub 2021 Mar 30.

Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA.

The C-terminal domain of Bacillus cereus hemolysin II (HlyIIC), stabilizes the trans-membrane-pore formed by the HlyII toxin and may aid in target cell recognition. Initial efforts to determine the NMR structure of HlyIIC were hampered by cis/trans isomerization about the single proline at position 405 that leads to doubling of NMR resonances. We used the mutant P405M-HlyIIC that eliminates the cis proline to determine the NMR structure of the domain, which revealed a novel fold. Read More

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Post-translationally modified conopeptides: Biological activities and pharmacological applications.

Elsie C Jimenez

Peptides 2021 May 5;139:170525. Epub 2021 Mar 5.

Department of Physical Sciences, College of Science, University of the Philippines Baguio, Baguio City, 2600, Philippines. Electronic address:

Conus venoms comprise a large variety of biologically active peptides (conopeptides or conotoxins) that are employed for prey capture and other biological functions. Throughout the course of evolution of the cone snails, they have developed an envenomation scheme that necessitates a potent mixture of peptides, most of which are highly post-translationally modified, that can cause rapid paralysis of their prey. The great diversity of these peptides defines the ecological interactions and evolutionary strategy of cone snails. Read More

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BcfH Is a Trimeric Thioredoxin-Like Bifunctional Enzyme with Both Thiol Oxidase and Disulfide Isomerase Activities.

Antioxid Redox Signal 2021 Apr 12. Epub 2021 Apr 12.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia.

Thioredoxin (TRX)-fold proteins are ubiquitous in nature. This redox scaffold has evolved to enable a variety of functions, including redox regulation, protein folding, and oxidative stress defense. In bacteria, the TRX-like disulfide bond (Dsb) family mediates the oxidative folding of multiple proteins required for fitness and pathogenic potential. Read More

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Hydration-Induced Structural Transitions in Biomimetic Tandem Repeat Proteins.

J Phys Chem B 2021 03 17;125(8):2134-2145. Epub 2021 Feb 17.

Faculty of Chemistry and Pharmacy, Department of Chemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.

A major challenge in developing biomimetic, high-performance, and sustainable products is the accurate replication of the biological materials' striking properties, such as high strength, self-repair, and stimuli-responsiveness. The rationalization of such features on the microscopic scale, together with the rational design of synthetic materials, is currently hindered by our limited understanding of the sequence-structure-property relationship. Here, employing state-of-the-art nuclear magnetic resonance (NMR) spectroscopy, we link the atomistic structural and dynamic properties of an artificial bioinspired tandem repeat protein TR(1,11) to its stunning macroscopic properties including high elasticity, self-healing capabilities, and record-holding proton conductivity among biological materials. Read More

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p53 Is Potentially Regulated by Cyclophilin D in the Triple-Proline Loop of the DNA Binding Domain.

Biochemistry 2021 Mar 16;60(8):597-606. Epub 2021 Feb 16.

The multifunctional protein p53 is the central molecular sensor of cellular stresses. The canonical function of p53 is to transcriptionally activate target genes in response to, for example, DNA damage that may trigger apoptosis. Recently, p53 was also found to play a role in the regulation of necrosis, another type of cell death featured by the mitochondrial permeability transition (mPT). Read More

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Transcriptional profiling of fission yeast RNA polymerase II CTD mutants.

RNA 2021 Feb 12. Epub 2021 Feb 12.

Sloan Kettering Institute;

The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol2) consists of tandem repeats of a consensus heptapeptide Y S P T S P S The CTD recruits numerous proteins that drive or regulate gene expression. The trafficking of CTD-interacting proteins is orchestrated by remodeling CTD primary structure via Ser/Thr/Tyr phosphorylation and proline isomerization, which collectively inscribe a CTD code. The fission yeast CTD consists of 29 heptad repeats. Read More

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February 2021

Epigenetic regulation and promising therapies in colorectal cancer.

Chandra Kishore

Curr Mol Pharmacol 2021 Jan 25. Epub 2021 Jan 25.

Department of Biotechnology, Indian Institute of Technology Madras, Life Science Building, Fatki Kutti, Madhepur, Madhubani, Patna-847408, Bihar. India.

The recent developments in epigenetics have shown a very important role of epigenetic changes in cancer initiation, development, and progression. Some of the important histone modifications shown to occur are methylation, acetylation, phosphorylation, citrullination, sumoylation, ADP ribosylation, deamination, ubiquitination, formylation, O-GlcNAcylation, propionylation, butyrylation, proline isomerization, and crotonylation but most of the studies in past had limited their studies mainly on histone methylation, acetylation, and phosphorylation. Modification of DNA strand by hypermethylation and hypomethylation regulates genomic instability and promotes cancer. Read More

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January 2021

Cohesin-dockerin code in cellulosomal dual binding modes and its allosteric regulation by proline isomerization.

Structure 2021 Feb 2. Epub 2021 Feb 2.

Department of Chemistry and Center for NanoScience, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13 Haus E, 81377 München, Germany.

Cellulose is the most abundant organic molecule on Earth and represents a renewable and practically everlasting feedstock for the production of biofuels and chemicals. Self-assembled owing to the high-affinity cohesin-dockerin interaction, cellulosomes are huge multi-enzyme complexes with unmatched efficiency in the degradation of recalcitrant lignocellulosic substrates. The recruitment of diverse dockerin-borne enzymes into a multicohesin protein scaffold dictates the three-dimensional layout of the complex, and interestingly two alternative binding modes have been proposed. Read More

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February 2021

Enhancement of the Isomerization Activity and Thermostability of Cellobiose 2-Epimerase from by Exchange of a Flexible Loop.

J Agric Food Chem 2021 Feb 4;69(6):1907-1915. Epub 2021 Feb 4.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Cellobiose 2-epimerase (CE) offers a promising enzymatic approach to produce lactulose. However, its application is limited by the unsatisfactory isomerization activity and thermostability. Our study attempted to optimize the catalytic performances of CEs by flexible loop exchange, for which four mutants were constructed using CE (CE from ) as a template. Read More

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February 2021

Detecting aspartate isomerization and backbone cleavage after aspartate in intact proteins by NMR spectroscopy.

J Biomol NMR 2021 Jan 21;75(1):71-82. Epub 2021 Jan 21.

Christian Doppler Laboratory for Innovative Tools for Biosimilar Characterization, University of Salzburg, Hellbrunnerstrasse 34, 5020, Salzburg, Austria.

The monitoring of non-enzymatic post-translational modifications (PTMs) in therapeutic proteins is important to ensure drug safety and efficacy. Together with methionine and asparagine, aspartic acid (Asp) is very sensitive to spontaneous alterations. In particular, Asp residues can undergo isomerization and peptide-bond hydrolysis, especially when embedded in sequence motifs that are prone to succinimide formation or when followed by proline (Pro). Read More

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January 2021

Enantiopure 5-CF-Proline: Synthesis, Incorporation in Peptides, and Tuning of the Peptide Bond Geometry.

Org Lett 2021 Jan 28;23(2):382-387. Epub 2020 Dec 28.

CNRS, BioCIS, CY Cergy Paris Université, 95000 Cergy Pontoise, France.

The straightforward synthesis of enantiopure 5-()-and 5-()-trifluoromethylproline is reported. The key steps are a Ruppert-Prakash reagent addition on l-pyroglutamic esters followed by an elimination reaction and a selective reduction. The solution-phase and solid-phase incorporation of this unprotected enantiopure fluorinated amino acid in a short peptide chain was demonstrated. Read More

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January 2021

Proline isomerization effects in the amyloidogenic protein β-microglobulin.

Phys Chem Chem Phys 2021 Jan;23(1):356-367

CNR-Nano S3, via Campi 215/a, Modena, Italy and Department of Chemical Sciences, University of Padova, Via Marzolo 1, Padova, Italy.

The protein β2-microglobulin (β2-m) can aggregate in insoluble amyloid fibrils, which deposit in the skeletal muscle system of patients undergoing long-term haemodialysis. The molecular mechanisms of such amyloidogenesis are still not fully understood. A potential, although debated, triggering factor is the cis to trans isomerization of a specific proline (Pro32) in β2-m. Read More

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January 2021

Prolyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel.

Nat Commun 2020 12 16;11(1):6401. Epub 2020 Dec 16.

Weill Cornell Medicine, Department of Anesthesiology, 1300 York Avenue, New York, NY, 10065, USA.

SthK, a cyclic nucleotide-modulated ion channel from Spirochaeta thermophila, activates slowly upon cAMP increase. This is reminiscent of the slow, cAMP-induced activation reported for the hyperpolarization-activated and cyclic nucleotide-gated channel HCN2 in the family of so-called pacemaker channels. Here, we investigate slow cAMP-induced activation in purified SthK channels using stopped-flow assays, mutagenesis, enzymatic catalysis and inhibition assays revealing that the cis/trans conformation of a conserved proline in the cyclic nucleotide-binding domain determines the activation kinetics of SthK. Read More

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December 2020

Catalysis of proline isomerization and molecular chaperone activity in a tug-of-war.

Nat Commun 2020 11 27;11(1):6046. Epub 2020 Nov 27.

German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075, Göttingen, Germany.

Catalysis of cis/trans isomerization of prolines is important for the activity and misfolding of intrinsically disordered proteins. Catalysis is achieved by peptidylprolyl isomerases, a superfamily of molecular chaperones. Here, we provide atomic insight into a tug-of-war between cis/trans isomerization and molecular chaperone activity. Read More

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November 2020

Diverse and conserved roles of the protein Ssu72 in eukaryotes: from yeast to higher organisms.

Curr Genet 2021 Apr 26;67(2):195-206. Epub 2020 Nov 26.

Department of Interventional Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.

Gene transcription is a complex biological process that involves a set of factors, enzymes and nucleotides. Ssu72 plays a crucial role in every step of gene transcription. RNA polymerase II (RNAPII) occupies an important position in the synthesis of mRNAs. Read More

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Plant Cyclophilins: Multifaceted Proteins With Versatile Roles.

Front Plant Sci 2020 22;11:585212. Epub 2020 Oct 22.

Department of Biotechnology, Guru Nanak Dev University, Amritsar, India.

Cyclophilins constitute a family of ubiquitous proteins that bind cyclosporin A (CsA), an immunosuppressant drug. Several of these proteins possess peptidyl-prolyl isomerase (PPIase) activity that catalyzes the isomerization of the peptide bond preceding a proline residue, essential for correct folding of the proteins. Compared to prokaryotes and other eukaryotes studied until now, the cyclophilin gene families in plants exhibit considerable expansion. Read More

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October 2020

The Peptidyl-prolyl Isomerase Pin1 in Neuronal Signaling: from Neurodevelopment to Neurodegeneration.

Mol Neurobiol 2021 Mar 21;58(3):1062-1073. Epub 2020 Oct 21.

Department of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100, Pavia, Italy.

The peptidyl-prolyl isomerase Pin1 is a unique enzyme catalyzing the isomerization of the peptide bond between phosphorylated serine-proline or threonine-proline motifs in proteins, thereby regulating a wide spectrum of protein functions, including folding, intracellular signaling, transcription, cell cycle progression, and apoptosis. Pin1 has been reported to act as a key molecular switch inducing cell-type-specific effects, critically depending on the different phosphorylation patterns of its targets within different biological contexts. While its implication in proliferating cells, and, in particular, in the field of cancer, has been widely characterized, less is known about Pin1 biological functions in terminally differentiated and post-mitotic neurons. Read More

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The influence of proline isomerization on potency and stability of anti-HIV antibody 10E8.

Sci Rep 2020 08 31;10(1):14313. Epub 2020 Aug 31.

Department of Medicinal Chemistry, University of Washington, Seattle, WA, 98195, USA.

Monoclonal antibody (mAb) 10E8 recognizes a highly conserved epitope on HIV and is capable of neutralizing > 95% of circulating viral isolates making it one of the most promising Abs against HIV. Solution instability and biochemical heterogeneity of 10E8 has hampered its development for clinical use. We identify the source of 10E8 heterogeneity being linked to cis/trans isomerization at two prolines within the YPP motif in the CRD3 loop that exists as two predominant conformers that interconvert on a slow timescale. Read More

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Deletion of a Peptidylprolyl Isomerase Gene Results in the Inability of To Grow on Crystalline Cellulose without Affecting Protein Glycosylation or Growth on Soluble Substrates.

Appl Environ Microbiol 2020 10 1;86(20). Epub 2020 Oct 1.

Genetics Department, University of Georgia, Athens, Georgia, USA

secretes a large number of complementary multifunctional enzymes with unique activities for biomass deconstruction. The most abundant enzymes in the secretome are found in a unique gene cluster containing a glycosyl transferase (GT39) and a putative peptidyl prolyl isomerase. Deletion of the glycosyl transferase in this cluster resulted in loss of detectable protein glycosylation in , and its activity has been shown to be responsible for the glycosylation of the proline-threonine rich linkers found in many of the multifunctional cellulases. Read More

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October 2020

Refolding of Cold-Denatured Barstar Induced by Radio-Frequency Heating: A New Method to Study Protein Folding by Real-Time NMR Spectroscopy.

Angew Chem Int Ed Engl 2020 12 25;59(49):22086-22091. Epub 2020 Sep 25.

Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-Universität Frankfurt, Max-von-Laue-Str. 7, 60438, Frankfurt, Germany.

The C40A/C82A double mutant of barstar has been shown to undergo cold denaturation above the water freezing point. By rapidly applying radio-frequency power to lossy aqueous samples, refolding of barstar from its cold-denatured state can be followed by real-time NMR spectroscopy. Since temperature-induced unfolding and refolding is reversible for this double mutant, multiple cycling can be utilized to obtain 2D real-time NMR data. Read More

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December 2020

Auxin-transporting ABC transporters are defined by a conserved D/E-P motif regulated by a prolylisomerase.

J Biol Chem 2020 09 22;295(37):13094-13105. Epub 2020 Jul 22.

Department of Biology, University of Fribourg, Fribourg, Switzerland. Electronic address:

The plant hormone auxin must be transported throughout plants in a cell-to-cell manner to affect its various physiological functions. ABCB transporters are critical for this polar auxin distribution, but the regulatory mechanisms controlling their function is not fully understood. The auxin transport activity of ABCB1 was suggested to be regulated by a physical interaction with FKBP42/Twisted Dwarf1 (TWD1), a peptidylprolyl isomerase (PPIase), but all attempts to demonstrate such a PPIase activity by TWD1 have failed so far. Read More

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September 2020

Mechanistic study of PDIA1-catalyzed TFF3 dimerization during sepsis.

Life Sci 2020 Aug 23;255:117841. Epub 2020 May 23.

Clinical Medical Research Center, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Army Medical University, Chongqing 400038, China; Department of Burns, Union Hospital, Fujian Medical University, Fuzhou 350001, China; Shriners Burns Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America. Electronic address:

Aims: Trefoil factor 3 (TFF3) is a gut mucosal protective molecule that is secreted by intestinal goblet cells. The dimeric structure of TFF3 enables it to function in intestinal mucosal repair and to maintain its own stability. Protein disulfide isomerase a1 (PDIA1) can directly catalyze the formation, isomerization and reduction of disulfide bonds in proteins and may play an important role in the formation of TFF3 dimer. Read More

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Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR's Anti-apoptotic Function at Mitochondria, and the Implications in Cancer.

Front Cell Dev Biol 2020 30;8:281. Epub 2020 Apr 30.

Department of Cancer Biology, University of Toledo College of Medicine, Toledo, OH, United States.

Peptidyl-prolyl isomerization is an important post-translational modification of protein because proline is the only amino acid that can stably exist as and , while other amino acids are in the conformation in protein backbones. This makes prolyl isomerization a unique mechanism for cells to control many cellular processes. Isomerization is a rate-limiting process that requires a peptidyl-prolyl / isomerase (PPIase) to overcome the energy barrier between and isomeric forms. Read More

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PIN1 Provides Dynamic Control of MYC in Response to Extrinsic Signals.

Front Cell Dev Biol 2020 2;8:224. Epub 2020 Apr 2.

Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, OR, United States.

PIN1 is a phosphorylation-directed member of the peptidyl-prolyl / isomerase (PPIase) family that facilitates conformational changes in phosphorylated targets such as c-MYC (MYC). Following signaling events that mediate phosphorylation of MYC at Serine 62, PIN1 establishes structurally distinct pools of MYC through its and isomerization activity at Proline 63. Through these isomerization steps, PIN1 functionally regulates MYC's stability, the molecular timing of its DNA binding and transcriptional activity, and its subnuclear localization. Read More

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Prolyl Isomerase Pin1 in Human Cancer: Function, Mechanism, and Significance.

Front Cell Dev Biol 2020 31;8:168. Epub 2020 Mar 31.

Laboratory of Molecular Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Collaborative Innovation Center of Biotherapy, Chengdu, China.

Peptidyl-prolyl isomerase NIMA-interacting 1 (Pin1) is an evolutionally conserved and unique enzyme that specifically catalyzes the isomerization of phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif and, subsequently, induces the conformational change of its substrates. Mounting evidence has demonstrated that Pin1 is widely overexpressed and/or overactivated in cancer, exerting a critical influence on tumor initiation and progression via regulation of the biological activity, protein degradation, or nucleus-cytoplasmic distribution of its substrates. Moreover, Pin1 participates in the cancer hallmarks through activating some oncogenes and growth enhancers, or inactivating some tumor suppressors and growth inhibitors, suggesting that Pin1 could be an attractive target for cancer therapy. Read More

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Calnexin cycle - structural features of the ER chaperone system.

FEBS J 2020 Oct 27;287(20):4322-4340. Epub 2020 Apr 27.

From the Department of Biochemistry & Centre for Structural Biology, McGill University, Montréal, QC, Canada.

The endoplasmic reticulum (ER) is the major folding compartment for secreted and membrane proteins and is the site of a specific chaperone system, the calnexin cycle, for folding N-glycosylated proteins. Recent structures of components of the calnexin cycle have deepened our understanding of quality control mechanisms and protein folding pathways in the ER. In the calnexin cycle, proteins carrying monoglucosylated glycans bind to the lectin chaperones calnexin and calreticulin, which recruit a variety of function-specific chaperones to mediate protein disulfide formation, proline isomerization, and general protein folding. Read More

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October 2020

Genetic interactions and transcriptomics implicate fission yeast CTD prolyl isomerase Pin1 as an agent of RNA 3' processing and transcription termination that functions via its effects on CTD phosphatase Ssu72.

Nucleic Acids Res 2020 05;48(9):4811-4826

Dept. of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.

The phosphorylation pattern of Pol2 CTD Y1S2P3T4S5P6S7 repeats comprises an informational code coordinating transcription and RNA processing. cis-trans isomerization of CTD prolines expands the scope of the code in ways that are not well understood. Here we address this issue via analysis of fission yeast peptidyl-prolyl isomerase Pin1. Read More

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Pinning Down the Transcription: A Role for Peptidyl-Prolyl Isomerase Pin1 in Gene Expression.

Front Cell Dev Biol 2020 20;8:179. Epub 2020 Mar 20.

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

Pin1 is a peptidyl-prolyl isomerase that specifically binds to a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif and catalyzes the isomerization of proline imidic peptide bond, resulting in conformational change of its substrates. Pin1 regulates many biological processes and is also involved in the development of human diseases, like cancer and neurological diseases. Many Pin1 substrates are transcription factors and transcription regulators, including RNA polymerase II (RNAPII) and factors associated with transcription initiation, elongation, termination and post-transcription mRNA decay. Read More

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