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Post translational modification

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https://www.readbyqxmd.com/read/29223644/functional-significance-of-o-glcnac-modification-in-regulating-neuronal-properties
#1
REVIEW
Hongik Hwang, Hyewhon Rhim
Post-translational modifications (PTMs) covalently modify proteins and diversify protein functions. Along with protein phosphorylation, another common PTM is the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and/or threonine residues. O-GlcNAc modification is similar to phosphorylation in that it occurs to serine and threonine residues and cycles on and off with a similar time scale. However, a striking difference is that the addition and removal of the O-GlcNAc moiety on all substrates are mediated by the two enzymes regardless of proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively...
December 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29221594/periodontal-disease-and-periodontal-bacteria-as-triggers-for-rheumatoid-arthritis
#2
REVIEW
Zijian Cheng, Josephine Meade, Kulveer Mankia, Paul Emery, Deirdre A Devine
There is an epidemiological association between periodontitis and rheumatoid arthritis (RA), which is hypothesised to lead to enhanced generation of RA-related autoantibodies that can be detected years before the onset of RA symptoms. Periodontitis is a common dysbiotic disease; tissue damage occurs because the immune system fails to limit both the resident microbial community and the associated local immune response. Certain periodontal bacteria, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, may contribute to RA autoantibody production through direct post-translational modification of proteins or, indirectly, by influencing neutrophil-mediated neo-epitope generation...
February 2017: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/29220647/snapshot-lysine-methylation-beyond-histones
#3
Kyle K Biggar, Zhentian Wang, Shawn S-C Li
Lysine methylation is a prevalent post-translational modification (PTM) used by the cell to reversibly regulate protein function. Although it has been extensively studied in the context of histones and the associated chromatin, the remaining methyllysine proteome remains largely unexplored. This SnapShot provides an overview of the current state of lysine methylation research and its emergence as a dynamic PTM occurring on histone and non-histone proteins.
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29220464/kipho-malaria-parasite-kinome-and-phosphatome-portal
#4
Rajan Pandey, Pawan Kumar, Dinesh Gupta
The Plasmodium kinases and phosphatases play an essential role in the regulation of substrate reversible-phosphorylation and overall cellular homeostasis. Reversible phosphorylation is one of the key post-translational modifications (PTMs) essential for parasite survival. Thus, a complete and comprehensive information of malarial kinases and phosphatases as a single web resource will not only aid in systematic and better understanding of the PTMs, but also facilitate efforts to look for novel drug targets for malaria...
January 1, 2017: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/29216821/molecular-targets-and-signaling-pathways-regulated-by-nuclear-translocation-of-syndecan-1
#5
Tünde Szatmári, Filip Mundt, Ashish Kumar-Singh, Lena Möbus, Rita Ötvös, Anders Hjerpe, Katalin Dobra
BACKGROUND: The cell-surface heparan sulfate proteoglycan syndecan-1 is important for tumor cell proliferation, migration, and cell cycle regulation in a broad spectrum of malignancies. Syndecan-1, however, also translocates to the cell nucleus, where it might regulate various molecular functions. RESULTS: We used a fibrosarcoma model to dissect the functions of syndecan-1 related to the nucleus and separate them from functions related to the cell-surface. Nuclear translocation of syndecan-1 hampered the proliferation of fibrosarcoma cells compared to the mutant lacking nuclear localization signal...
December 8, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29216372/the-c-terminal-domain-of-p53-orchestrates-the-interplay-between-non-covalent-and-covalent-poly-adp-ribosyl-ation-of-p53-by-parp1
#6
Arthur Fischbach, Annika Krüger, Stephanie Hampp, Greta Assmann, Lisa Rank, Matthias Hufnagel, Martin T Stöckl, Jan M F Fischer, Sebastian Veith, Pascal Rossatti, Magdalena Ganz, Elisa Ferrando-May, Andrea Hartwig, Karin Hauser, Lisa Wiesmüller, Alexander Bürkle, Aswin Mangerich
The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding and covalent PARylation control protein functions, however, it is unknown how the two modes of modification crosstalk mechanistically. Employing the tumor suppressor p53 as a model substrate, this study provides detailed insights into the interplay between non-covalent and covalent PARylation and unravels its functional significance in the regulation of p53...
December 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29215186/a-general-approach-towards-triazole-linked-adenosine-diphosphate-ribosylated-peptides-and-proteins
#7
Qiang Liu, Hans A V Kistemaker, Sagar Bhogaraju, Ivan Dikic, Herman S Overkleeft, Gijsbert A van der Marel, Huib Ovaa, Gerbrand van der Heden van Noort, Dmitri V Filippov
Current chemistries to prepare Adenosine Diphosphate ribosylated (ADPr) peptides are not generally applicable due to the labile nature of this post-translational modification and its incompatibility with strong acidic conditions used in standard solid phase peptide synthesis protocols. We present a general strategy to prepare ADPr peptide analogues based on a copper catalysed click reaction between an azide modified peptide and an alkyne modified ADPr counterpart. We expand the scope of this approach to proteins by preparing two ADPr Ubiquitin analogues carrying the biological relevant α-glycosidic linkage...
December 7, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29214870/advances-in-cell-free-protein-array-methods
#8
Xiaobo Yu, Brianne Petritis, Hu Duan, Danke Xu, Joshua LaBaer
Cell-free protein microarrays represent a special form of protein microarray which display proteins made fresh at the time of the experiment, avoiding storage and denaturation. They have been used increasingly in basic and translational research over the past decade to study protein-protein interactions, the pathogen-host relationship, post-translational modifications, and antibody biomarkers of different human diseases. Their role in the first blood-based diagnostic test for early stage breast cancer highlights their value in managing human health...
December 7, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/29214361/forcegen-atomic-covalent-bond-value-derivation-for-gromacs
#9
Anthony Nash, Thomas Collier, Helen L Birch, Nora H de Leeuw
A large number of crystallographic protein structures include ligands, small molecules and post-translational modifications. Atomic bond force values for computational atomistic models of post-translational or non-standard amino acids, metal binding active sites, small molecules and drug molecules are not readily available in most simulation software packages. We present ForceGen, a Java tool that extracts the bond stretch and bond angle force values and equilibrium values from the Hessian of a Gaussian vibrational frequency analysis...
December 6, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29213065/modulation-of-microtubule-acetylation-by-the-interplay-of-tppp-p25-sirt2-and-new-anticancer-agents-with-anti-sirt2-potency
#10
Adél Szabó, Judit Oláh, Sándor Szunyogh, Attila Lehotzky, Tibor Szénási, Marianna Csaplár, Matthias Schiedel, Péter Lőw, Manfred Jung, Judit Ovádi
The microtubule network exerts multifarious functions controlled by its decoration with various proteins and post-translational modifications. The disordered microtubule associated Tubulin Polymerization Promoting Protein (TPPP/p25) and the NAD+-dependent tubulin deacetylase sirtuin-2 (SIRT2) play key roles in oligodendrocyte differentiation by acting as dominant factors in the organization of myelin proteome. Herein, we show that SIRT2 impedes the TPPP/p25-promoted microtubule assembly independently of NAD+; however, the TPPP/p25-assembled tubulin ultrastructures were resistant against SIRT2 activity...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29213033/-epigenetic-modifications-of-chromatin-in-epilepsy-a-potential-mechanism-of-pharmacoresistance
#11
L S Sokhranyaeva, V A Aniol, N V Gulyaeva
Pharmacoresistance in epilepsy is an important problem from both clinical and fundamental perspectives. The existent hypotheses of pharmacoresistance are based on long term plastic rebuilding of the epileptic brain. One of potential mechanisms mediating such protracted changes are alterations of gene expression induced by epigenetic modifications of chromatin in brain cells of epileptic patients. Recently, changes in DNA methylation and histone post-translational modifications were reported in brain tissues of patients with pharmacoresistant epilepsy...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29212943/the-cellular-chaperone-heat-shock-protein-90-is-required-for-foot-and-mouth-disease-virus-capsid-precursor-processing-and-assembly-of-capsid-pentamers
#12
Joseph Newman, Amin S Asfor, Stephen Berryman, Terry Jackson, Stephen Curry, Tobias J Tuthill
Productive picornavirus infection requires the hijack of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerisation of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and post-translational modification of the capsid precursor (P1-2A) by viral and cellular enzymes, and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212224/hadc5-deacetylates-mkl1-to-dampen-tnf-%C3%AE-induced-pro-inflammatory-gene-transcription-in-macrophages
#13
Zilong Li, Hao Qin, Jianfei Li, Liming Yu, Yuyu Yang, Yong Xu
Macrophage-dependent inflammatory response on the one hand functions as a key line of defense in host immunity but on the other hand underlies the pathogenesis of a host of human pathologies when aberrantly activated. Our previous investigations have led to the identification of megakaryocytic leukemia 1 (MKL1) as a key co-factor of NF-κB/p65 participating in TNF-α induced pro-inflammatory transcription in macrophages. How post-translational modifications contribute to the modulation of MKL1 activity remains an underexplored subject matter...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211989/allosteric-control-of-a-plant-receptor-kinase-through-s-glutathionylation
#14
Alexander S Moffett, Kyle W Bender, Steven C Huber, Diwakar Shukla
Growing evidence supports the importance of protein S-glutathionylation as a regulatory post-translational modification with functional consequences for proteins. Discoveries of redox-state-dependent protein kinase S-glutathionylation have fueled discussion of redox-sensitive signaling. Following previously published experimental evidence for S-glutathionylation induced deactivation of the Arabidopsis thaliana kinase BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR-LIKE KINASE 1 (BAK1), we investigated the consequences of S-glutathionylation on the equilibrium conformational ensemble of BAK1 using all-atom molecular dynamics simulations...
December 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29211738/metformin-inhibits-the-development-and-promotes-the-resensitization-of-treatment-resistant-breast-cancer
#15
Gerald Davies, Liubov Lobanova, Wojciech Dawicki, Gary Groot, John R Gordon, Matthew Bowen, Troy Harkness, Terra Arnason
Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors...
2017: PloS One
https://www.readbyqxmd.com/read/29208956/pol%C3%AE-o-glcnacylation-governs-genome-integrity-during-translesion-dna-synthesis
#16
Xiaolu Ma, Hongmei Liu, Jing Li, Yihao Wang, Yue-He Ding, Hongyan Shen, Yeran Yang, Chenyi Sun, Min Huang, Yingfeng Tu, Yang Liu, Yongliang Zhao, Meng-Qiu Dong, Ping Xu, Tie-Shan Tang, Caixia Guo
DNA polymerase η (Polη) facilitates translesion DNA synthesis (TLS) across ultraviolet (UV) irradiation- and cisplatin-induced DNA lesions implicated in skin carcinogenesis and chemoresistant phenotype formation, respectively. However, whether post-translational modifications of Polη are involved in these processes remains largely unknown. Here, we reported that human Polη undergoes O-GlcNAcylation at threonine 457 by O-GlcNAc transferase upon DNA damage. Abrogation of this modification results in a reduced level of CRL4CDT2-dependent Polη polyubiquitination at lysine 462, a delayed p97-dependent removal of Polη from replication forks, and significantly enhanced UV-induced mutagenesis even though Polη focus formation and its efficacy to bypass across cyclobutane pyrimidine dimers after UV irradiation are not affected...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29207274/causes-and-consequences-of-microtubule-acetylation
#17
REVIEW
Carsten Janke, Guillaume Montagnac
Among the different types of cytoskeletal components, microtubules arguably accumulate the greatest diversity of post-translational modifications (PTMs). Acetylation of lysine 40 (K40) of α-tubulin has received particular attention because it is the only tubulin PTM to be found in the lumen of microtubules: most other tubulin PTMs are found at the outer surface of the microtubule. As a consequence, the enzyme catalyzing K40 acetylation needs to penetrate the narrow microtubule lumen to find its substrate. Acetylated microtubules have been considered to be stable, long-lived microtubules; however, until recently, there was little information about whether the longevity of these microtubules is the cause or the consequence of acetylation...
December 4, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29206923/vascular-abnormalities-in-the-placenta-of-chst14-fetuses-implications-in-the-pathophysiology-of-perinatal-lethality-of-the-murine-model-and-vascular-lesions-in-human-chst14-d4st1-deficiency
#18
Takahiro Yoshizawa, Shuji Mizumoto, Yuki Takahashi, Shin Shimada, Kazuyuki Sugahara, Jun Nakayama, Shin'ichi Takeda, Yoshihiro Nomura, Yuko Nitahara-Kasahara, Takashi Okada, Kiyoshi Matsumoto, Shuhei Yamada, Tomoki Kosho
Collagen is one of the most important components of the extracellular matrix that is involved in the strength of tissues, cell adhesion, and cell proliferation. Mutations in several collagen and post-translational modification enzyme genes cause Ehlers-Danlos syndrome (EDS) characterized by joint and skin hyperextensibility as well as fragility of various organs. Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) is a critical enzyme for biosynthesis of dermatan sulfate, a side chain of various proteoglycans including biglycan that regulates collagen fibrils through their interaction...
December 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/29205438/towards-the-identification-of-reliable-sperm-biomarkers-for-male-infertility-a-sperm-proteomic-approach
#19
P Intasqui, A Agarwal, R Sharma, L Samanta, R P Bertolla
Male infertility evaluation is mainly based on semen analysis. Thus, identification of additional diagnostic methods is valuable. The aim of this study was to analyse the sperm proteome of infertile men to identify the underlying mechanisms and reliable diagnostic biomarkers. This cross-sectional study consisted of 16 infertile men and seven proven fertile men. An LC-MS/MS approach was performed in five pooled samples of each group (proven fertile men, primary infertility and secondary infertility). Differentially expressed proteins were used for functional enrichment analyses, and the most central proteins involved in altered functions in both infertile groups and the testis-specific proteins were validated using Western blotting and immunocytochemistry...
December 4, 2017: Andrologia
https://www.readbyqxmd.com/read/29204749/phosphorylation-of-pyridoxal-5-phosphate-enzymes-an-intriguing-and-neglected-topic
#20
REVIEW
Giada Rossignoli, Robert S Phillips, Alessandra Astegno, Marta Menegazzi, Carla Borri Voltattorni, Mariarita Bertoldi
Pyridoxal 5'-phosphate (PLP)-dependent enzymes catalyze a wide range of reactions of amino acids and amines, with the exception of glycogen phosphorylase which exhibits peculiar both substrate preference and chemical mechanism. They represent about 4% of the gene products in eukaryotic cells. Although structure-function investigations regarding these enzymes are copious, their regulation by post-translational modifications is largely unknown. Protein phosphorylation is the most common post-translational modification fundamental in mediating diverse cellular functions...
December 4, 2017: Amino Acids
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