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.

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 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 Identification and Characterization of HTLV-1 HBZ Post-Translational Modifications

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112762 ◽  
Author(s):  
Nathan Dissinger ◽  
Nikoloz Shkriabai ◽  
Sonja Hess ◽  
Jacob Al-Saleem ◽  
Mamuka Kvaratskhelia ◽  
...  
Keyword(s):  
Post Translational Modifications ◽  
Identification And Characterization

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.

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