Collagen hydroxylysine glycosylation: non-conventional substrates for atypical glycosyltransferase enzymes

2021 ◽  
Author(s):  
Francesca De Giorgi ◽  
Marco Fumagalli ◽  
Luigi Scietti ◽  
Federico Forneris
Keyword(s):  
Current Knowledge ◽  
Three Dimensional ◽  
Major Constituent ◽  
Post Translational Modifications ◽  
Current State ◽  
Lysine Residues ◽  
Collagen Molecules ◽  
Triple Helices ◽  
The Impact

Collagen is a major constituent of the extracellular matrix (ECM) that confers fundamental mechanical properties to tissues. To allow proper folding in triple-helices and organization in quaternary super-structures, collagen molecules require essential post-translational modifications (PTMs), including hydroxylation of proline and lysine residues, and subsequent attachment of glycan moieties (galactose and glucose) to specific hydroxylysine residues on procollagen alpha chains. The resulting galactosyl-hydroxylysine (Gal-Hyl) and less abundant glucosyl-galactosyl-hydroxylysine (Glc-Gal-Hyl) are amongst the simplest glycosylation patterns found in nature and are essential for collagen and ECM homeostasis. These collagen PTMs depend on the activity of specialized glycosyltransferase enzymes. Although their biochemical reactions have been widely studied, several key biological questions about the possible functions of these essential PTMs are still missing. In addition, the lack of three-dimensional structures of collagen glycosyltransferase enzymes hinders our understanding of the catalytic mechanisms producing this modification, as well as the impact of genetic mutations causing severe connective tissue pathologies. In this mini-review, we summarize the current knowledge on the biochemical features of the enzymes involved in the production of collagen glycosylations and the current state-of-the-art methods for the identification and characterization of this important PTM.

scholarly journals Super Secondary Structures of Proteins with Post-Translational Modifications in Colon Cancer

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3144
Author(s):  
Dmitry Tikhonov ◽  
Liudmila Kulikova ◽  
Arthur Kopylov ◽  
Kristina Malsagova ◽  
Alexander Stepanov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Control Cell ◽  
Three Dimensional ◽  
Vitamin D Binding Protein ◽  
High Throughput Analysis ◽  
Post Translational Modifications ◽  
New Strategy ◽  
The Impact ◽  
Identification And Characterization

New advances in protein post-translational modifications (PTMs) have revealed a complex layer of regulatory mechanisms through which PTMs control cell signaling and metabolic pathways, contributing to the diverse metabolic phenotypes found in cancer. Using conformational templates and the three-dimensional (3D) environment investigation of proteins in patients with colorectal cancer, it was demonstrated that most PTMs (phosphorylation, acetylation, and ubiquitination) are localized in the supersecondary structures (helical pairs). We showed that such helical pairs are represented on the outer surface of protein molecules and characterized by a largely accessible area for the surrounding solvent. Most promising and meaningful modifications were observed on the surface of vitamin D-binding protein (VDBP), complement C4-A (CO4A), X-ray repair cross-complementing protein 6 (XRCC6), Plasma protease C1 inhibitor (IC1), and albumin (ALBU), which are related to colorectal cancer developing. Based on the presented data, we propose the impact of the observed modifications in immune response, inflammatory reaction, regulation of cell migration, and promotion of tumor growth. Here, we suggest a computational approach in which high-throughput analysis for identification and characterization of PTM signature, associated with cancer metabolic reprograming, can be improved to prognostic value and bring a new strategy to the targeted therapy.

scholarly journals Flowering plant embryos: How did we end up here?

2021 ◽  
Author(s):  
Stefan A. Rensing ◽  
Dolf Weijers
Keyword(s):  
Current Knowledge ◽  
General Structure ◽  
Three Dimensional ◽  
Flowering Plants ◽  
Flowering Plant ◽  
Adult Plant ◽  
Ancestral State ◽  
Evolutionary Trajectory ◽  
Current State ◽  
Plant Embryo

AbstractThe seeds of flowering plants are sexually produced propagules that ensure dispersal and resilience of the next generation. Seeds harbor embryos, three dimensional structures that are often miniatures of the adult plant in terms of general structure and primordial organs. In addition, embryos contain the meristems that give rise to post-embryonically generated structures. However common, flowering plant embryos are an evolutionary derived state. Flowering plants are part of a much larger group of embryo-bearing plants, aptly termed Embryophyta. A key question is what evolutionary trajectory led to the emergence of flowering plant embryos. In this opinion, we deconstruct the flowering plant embryo and describe the current state of knowledge of embryos in other plant lineages. While we are far yet from understanding the ancestral state of plant embryogenesis, we argue what current knowledge may suggest and how the knowledge gaps may be closed.

scholarly journals Susceptibility of protein therapeutics to spontaneous chemical modifications by oxidation, cyclization, and elimination reactions

Amino Acids ◽  
2019 ◽  
Vol 51 (10-12) ◽  
pp. 1409-1431 ◽  
Author(s):  
Luigi Grassi ◽  
Chiara Cabrele
Keyword(s):  
Small Molecules ◽  
Three Dimensional ◽  
Drug Market ◽  
Structure And Function ◽  
Dimensional Structure ◽  
Chemical Modifications ◽  
Small Molecule Drugs ◽  
And Function ◽  
The Impact

Abstract Peptides and proteins are preponderantly emerging in the drug market, as shown by the increasing number of biopharmaceutics already approved or under development. Biomolecules like recombinant monoclonal antibodies have high therapeutic efficacy and offer a valuable alternative to small-molecule drugs. However, due to their complex three-dimensional structure and the presence of many functional groups, the occurrence of spontaneous conformational and chemical changes is much higher for peptides and proteins than for small molecules. The characterization of biotherapeutics with modern and sophisticated analytical methods has revealed the presence of contaminants that mainly arise from oxidation- and elimination-prone amino-acid side chains. This review focuses on protein chemical modifications that may take place during storage due to (1) oxidation (methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine), (2) intra- and inter-residue cyclization (aspartic and glutamic acid, asparagine, glutamine, N-terminal dipeptidyl motifs), and (3) β-elimination (serine, threonine, cysteine, cystine) reactions. It also includes some examples of the impact of such modifications on protein structure and function.

scholarly journals The impact of contrast-enhanced spectral mammogram (CESM) and three-dimensional breast ultrasound (3DUS) on the characterization of the disease extend in cancer patients

2018 ◽  
pp. 20170977 ◽  
Author(s):  
Maha Hussien Helal ◽  
Sahar Mahmoud Mansour ◽  
Lamia Adel Salaleldin ◽  
Basma Mohamed Alkalaawy ◽  
Dorria Saleh Salem ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Three Dimensional ◽  
Breast Ultrasound ◽  
Contrast Enhanced ◽  
The Impact

scholarly journals Expression, purification and crystallization of a protein resulting from the inversion of the amino-acid sequence of a helical bundle

2017 ◽  
Vol 73 (1) ◽  
pp. 51-53
Author(s):  
Aikaterini Kefala ◽  
Dina Kotsifaki ◽  
Mary Providaki ◽  
Maria Amprazi ◽  
Michael Kokkinidis
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Three Dimensional ◽  
Unfolded Proteins ◽  
Unit Cell Parameters ◽  
Cell Parameters ◽  
Helical Bundle ◽  
Sequence Inversion ◽  
The Impact

Earlier studies have found that the occurrence of inverse sequence identity in proteins is not indicative of three-dimensional similarity, but rather leads to different folds or unfolded proteins. Short helices, however, frequently keep their conformations when their sequences are inverted. To explore the impact of sequence inversion on long helices, revRM6, with the inverse amino-acid sequence relative to RM6, a highly stable variant of the ColE1 Rop protein, was engineered. RM6 is a highly regular four-α-helical bundle that serves as a model system for protein-folding studies. Here, the crystallization and preliminary crystallographic characterization of revRM6 are reported. The protein was overexpressed inEscherichia coli, purified to homogeneity and crystallized. The crystals belonged to space groupP41212, with unit-cell parametersa=b= 44.98,c= 159.74 Å, and diffracted to a resolution of 3.45 Å.

scholarly journals A chemical screen identifies a link between lipid metabolism and mRNA translation

2020 ◽  
Author(s):  
Alba Corman ◽  
Dimitris C. Kanellis ◽  
Maria Häggblad ◽  
Vanesa Lafarga ◽  
Jiri Bartek ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Mrna Translation ◽  
Protein Translation ◽  
Sphingosine Kinases ◽  
Chemical Screen ◽  
Approved Drugs ◽  
The Impact

ABSTRACTmRNA translation is one of the most energy-demanding processes for living cells, alterations of which have been frequently documented in human disease. Using recently developed technologies that enable image-based quantitation of overall translation levels, we here conducted a chemical screen to evaluate how medically approved drugs, as well as drugs that are currently under development, influence overall translation levels. Consistent with current knowledge, inhibitors of the mTOR signaling pathway were the most represented class among translation suppresors. In addition, we identified that inhibitors of sphingosine kinases (SPHKs) also reduce mRNA translation levels independently of mTOR. Mechanistically this is explained by an effect of the compounds on the membranes of the endoplasmic reticulum, which activates the integrated stress response (ISR). Accordingly, the impact of SPHK inhibitors on translation is alleviated by the concomitant inhibition of ISR kinases. On the other hand, and despite the large number of molecules tested, our study failed to identify chemicals capable of substantially increasing mRNA translation, raising doubts on to what extent translation can be supra-physiologically stimulated in mammalian cells. In summary, our study provides the first comprehensive characterization of the effect of known drugs on protein translation and has helped to unravel a new link between lipid metabolism and mRNA translation in human cells.

scholarly journals Characterization of Histone Deacetylase Mechanisms in Cancer Development

2021 ◽  
Vol 11 ◽  
Author(s):  
Rihan Hai ◽  
Liuer He ◽  
Guang Shu ◽  
Gang Yin
Keyword(s):  
Histone Deacetylases ◽  
Histone Acetyltransferases ◽  
Cancer Development ◽  
Dynamic Processes ◽  
Tumour Suppressor Genes ◽  
Nonhistone Proteins ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Lysine Residues

Over decades of studies, accumulating evidence has suggested that epigenetic dysregulation is a hallmark of tumours. Post-translational modifications of histones are involved in tumour pathogenesis and development mainly by influencing a broad range of physiological processes. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are pivotal epigenetic modulators that regulate dynamic processes in the acetylation of histones at lysine residues, thereby influencing transcription of oncogenes and tumour suppressor genes. Moreover, HDACs mediate the deacetylation process of many nonhistone proteins and thus orchestrate a host of pathological processes, such as tumour pathogenesis. In this review, we elucidate the functions of HDACs in cancer.

scholarly journals SUMO proteins in the cardiovascular system: friend or foe?

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Prithviraj Manohar Vijaya Shetty ◽  
Ashraf Yusuf Rangrez ◽  
Norbert Frey
Keyword(s):  
Functional Group ◽  
Current Knowledge ◽  
Signalling Pathways ◽  
Small Peptides ◽  
Post Translational Modifications ◽  
Sumo Modification ◽  
Acetyl Group ◽  
The Impact ◽  
Small Chemical

Abstract Post-translational modifications (PTMs) are crucial for the adaptation of various signalling pathways to ensure cellular homeostasis and proper adaptation to stress. PTM is a covalent addition of a small chemical functional group such as a phosphate group (phosphorylation), methyl group (methylation), or acetyl group (acetylation); lipids like hydrophobic isoprene polymers (isoprenylation); sugars such as a glycosyl group (glycosylation); or even small peptides such as ubiquitin (ubiquitination), SUMO (SUMOylation), NEDD8 (neddylation), etc. SUMO modification changes the function and/or fate of the protein especially under stress conditions, and the consequences of this conjugation can be appreciated from development to diverse disease processes. The impact of SUMOylation in disease has not been monotonous, rather SUMO is found playing a role on both sides of the coin either facilitating or impeding disease progression. Several recent studies have implicated SUMO proteins as key regulators in various cardiovascular disorders. The focus of this review is thus to summarize the current knowledge on the role of the SUMO family in the pathophysiology of cardiovascular diseases.

scholarly journals Additive Manufacturing in the Construction Industry: The Comparative Competitiveness of 3D Concrete Printing

2021 ◽  
Vol 11 (9) ◽  
pp. 3865
Author(s):  
Siavash H. Khajavi ◽  
Müge Tetik ◽  
Ashish Mohite ◽  
Antti Peltokorpi ◽  
Mingyang Li ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Construction Industry ◽  
Positive Impact ◽  
Three Dimensional ◽  
Cost Effective ◽  
Robotic Arm ◽  
Process Time ◽  
Current State ◽  
The Cost ◽  
The Impact

The construction industry is facing increasing pressure to improve productivity and decrease its environmental impact. Additive manufacturing (AM) technologies, especially three-dimensional concrete printing (3DCP) technology, have provided many benefits for construction. However, holistic comparative studies of the competitiveness of 3DCP and conventional methods, from cost and time perspectives, are lacking. Choosing between the methods is difficult for practitioners. In this study, we investigated the current state of 3DCP in the construction industry using seven distinct scenarios. Our analysis was performed to illustrate the impact of design and supply chain configurations on performance. The results prove the notable competitiveness of 3DCP. In contrast to the conventional construction method, the more complex round design had a positive impact on the cost and process time in 3DCP scenarios. Additionally, we show that on-site 3DCP using a robotic arm was more cost-effective than off-site 3DCP.

Preparation and Characterization of Water Absorbing and Anti-Fogging Coatings

2016 ◽  
Vol 848 ◽  
pp. 722-725
Author(s):  
Kai Wang ◽  
Min Huang ◽  
Yue Huang ◽  
Zhong Hua Zhou ◽  
Shirley Shen
Keyword(s):  
Three Dimensional ◽  
Steam Bath ◽  
Structure Characterization ◽  
Hydroxyl Groups ◽  
Functional Coatings ◽  
Cure Reaction ◽  
Water Steam ◽  
Dimensional Network ◽  
The Impact

Anti-fogging functional coatings have a broad application prospective in the fields of construction and transportation vehicles. In this study, superior water absorbing and anti-fogging coatings were prepared by a cure reaction using epoxy resins as water absorbent resins, hydroxyethyl ethylenediamine as a curing agent, γ-ammonia propyl triethoxy silane as a coupling agent, organic silicon sol as filler. The impact of additional polyethylene glycol (PEG) on the properties of water absorbing and antifogging coating has also been studied. The anti-fogging experiments were conducted in a 40 °C water steam bath, and the result shows that the sample with additional 4.0 % PEG has an anti-fogging time of 315 seconds (s), which is better than that without PEG (the anti-fogging time being 240s). Infrared spectroscopy and scanning electron microscope structure characterization indicate that the sample with additional PEG has an obvious three-dimensional network structure with hydroxyl groups, which leads to a great saturated water quantity and a superior anti-fogging performance.

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