scholarly journals Photoregulation of PRMT-1 Using a Photolabile Non-Canonical Amino Acid

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5072
Author(s):  
Elizabeth A. King ◽  
Emily M. Peairs ◽  
Diya M. Uthappa ◽  
Jordan K. Villa ◽  
Cameron M. Goff ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Uv Light ◽  
Epigenetic Modification ◽  
Protecting Group ◽  
Methyltransferase Activity ◽  
Canonical Amino Acid ◽  
Protein Methyltransferases ◽  
And Control ◽  
Photolabile Protecting Group

Protein methyltransferases are vital to the epigenetic modification of gene expression. Thus, obtaining a better understanding of and control over the regulation of these crucial proteins has significant implications for the study and treatment of numerous diseases. One ideal mechanism of protein regulation is the specific installation of a photolabile-protecting group through the use of photocaged non-canonical amino acids. Consequently, PRMT1 was caged at a key tyrosine residue with a nitrobenzyl-protected Schultz amino acid to modulate protein function. Subsequent irradiation with UV light removes the caging group and restores normal methyltransferase activity, facilitating the spatial and temporal control of PRMT1 activity. Ultimately, this caged PRMT1 affords the ability to better understand the protein’s mechanism of action and potentially regulate the epigenetic impacts of this vital protein.

Transfer of chirality in N-triphenylacetylamino acids and chiral derivatives of N-triphenylacetyl Gly–Gly dipeptide and control of their assembly with steric constraints

CrystEngComm ◽  
2019 ◽  
Vol 21 (22) ◽  
pp. 3420-3430 ◽  
Author(s):  
Wioletta Bendzińska-Berus ◽  
Maciej Jelecki ◽  
Marcin Kwit ◽  
Urszula Rychlewska
Keyword(s):  
Amino Acid ◽  
Protecting Group ◽  
Peptide Derivatives ◽  
And Control ◽  
Derivatives Of ◽  
Steric Constraints

The N-triphenylacetyl group is utilized as a reporter of chirality and as a supramolecular protecting group for α-amino acid and peptide derivatives.

Reading the phosphorylation code: binding of the 14-3-3 protein to multivalent client phosphoproteins

2020 ◽  
Vol 477 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Nikolai N. Sluchanko
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Protein ◽  
Structural Basis ◽  
Major Protein ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Biochemical Journal ◽  
Multiple Binding ◽  
And Control

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.

Fluoroquinolone-3-carboxamide Amino Acid Conjugates: Synthesis, Antibacterial Properties And Molecular Modeling Studies

2020 ◽  
Vol 17 (1) ◽  
pp. 71-84
Author(s):  
Riham M. Bokhtia ◽  
Siva S. Panda ◽  
Adel S. Girgis ◽  
Hitesh H. Honkanadavar ◽  
Tarek S. Ibrahim ◽  
...  
Keyword(s):  
Experimental Data ◽  
Antibacterial Activity ◽  
Amino Acid ◽  
Bacterial Infections ◽  
Antibacterial Agents ◽  
Antibacterial Properties ◽  
Computational Studies ◽  
Protecting Group ◽  
Amino Acid Conjugates ◽  
Molecular Modeling Studies

Background: Bacterial infections are considered as one of the major global health threats, so it is very essential to design and develop new antibacterial agents to overcome the drawbacks of existing antibacterial agents. Method: The aim of this work is to synthesize a series of new fluoroquinolone-3-carboxamide amino acid conjugates by molecular hybridization. We utilized benzotriazole chemistry to synthesize the desired hybrid conjugates. Result: All the conjugates were synthesized in good yields, characterized, evaluated for their antibacterial activity. The compounds were screened for their antibacterial activity using methods adapted from the Clinical and Laboratory Standards Institute. Synthesized conjugates were tested for activity against medically relevant pathogens; Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27856) Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 19433). Conclusion: The observed antibacterial experimental data indicates the selectivity of our synthesized conjugates against E.Coli. The protecting group on amino acids decreases the antibacterial activity. The synthesized conjugates are non-toxic to the normal cell lines. The experimental data were supported by computational studies.

scholarly journals The Fungi-specific histone Acetyltransferase Rtt109 mediates morphogenesis, Aflatoxin synthesis and pathogenicity in Aspergillus flavus by acetylating H3K9

IMA Fungus ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruilin Sun ◽  
Meifang Wen ◽  
Lianghuan Wu ◽  
Huahui Lan ◽  
Jun Yuan ◽  
...  
Keyword(s):  
Aspergillus Flavus ◽  
Histone Acetyltransferase ◽  
Epigenetic Modification ◽  
Aerial Mycelium ◽  
Environmental Stress Response ◽  
New Thought ◽  
Conidium Formation ◽  
Complementary Strain ◽  
And Control ◽  
Yeast Extract Sucrose

AbstractAspergillus flavus is a common saprophytic filamentous fungus that produces the highly toxic natural compound aflatoxin during its growth process. Synthesis of the aflatoxins, which can contaminate food crops causing huge losses to the agricultural economy, is often regulated by epigenetic modification, such as the histone acetyltransferase. In this study, we used Aspergillus flavus as an experimental model to construct the acetyltransferase gene rtt109 knockout strain (△rtt109) and its complementary strain (△rtt109·com) by homologous recombination. The growth of △rtt109 was significantly suppressed compared to the wild type (WT) strain and the △rtt109·com strain. The sclerotium of △rtt109 grew smaller, and the amount of sclerotia generated by △rtt109 was significantly reduced. The number of conidiums of △rtt109 was significantly reduced, especially on the yeast extract sucrose (YES) solid medium. The amount of aflatoxins synthesized by △rtt109 in the PDB liquid medium was significantly decreased We also found that the △rtt109 strain was extremely sensitive to DNA damage stress. Through the maize seed infection experiment, we found that the growth of △rtt109 on the surface of affected corn was largely reduced, and the amount of aerial mycelium decreased significantly, which was consistent with the results on the artificial medium. We further found that H3K9 was the acetylated target of Rtt109 in A. flavus. In conclusion, Rtt109 participated in the growth, conidium formation, sclerotia generation, aflatoxin synthesis, environmental stress response, regulation of infection of A. flavus. The results from this study of rtt109 showed data for acetylation in the regulation of life processes and provided a new thought regarding the prevention and control of A. flavus hazards.

scholarly journals Avoided motifs: short amino acid strings missing from protein datasets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Function ◽  
Large Protein ◽  
New Approach ◽  
Cellular Context ◽  
Human Proteins ◽  
Context Specific ◽  
Protein Datasets

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.

scholarly journals The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erna Davydova ◽  
Tadahiro Shimazu ◽  
Maren Kirstin Schuhmacher ◽  
Magnus E. Jakobsson ◽  
Hanneke L. D. M. Willemen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Crucial Role ◽  
Complex I ◽  
Protein Modification ◽  
Zinc Binding ◽  
Functional Studies ◽  
Mitochondrial Respiratory Complex ◽  
Respiratory Complex I ◽  
Broad Specificity

AbstractPost-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.

scholarly journals Phylogenetic analysis and predicted functional effect of protein mutations of E6 and E7 HPV16 strains isolated in Indonesia

2015 ◽  
Vol 24 (4) ◽  
pp. 197-205
Author(s):  
Dwi Wulandari ◽  
Lisnawati Rachmadi ◽  
Tjahjani M. Sudiro
Keyword(s):  
Amino Acids ◽  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Asian American ◽  
Protein Function ◽  
Single Amino Acid ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
Neutral Mutations

Background: E6 and E7 are oncoproteins of HPV16. Natural amino acid variation in HPV16 E6 can alter its carcinogenic potential. The aim of this study was to analyze phylogenetically E6 and E7 genes and proteins of HPV16 from Indonesia and predict the effects of single amino acid substitution on protein function. This analysis could be used to reduce time, effort, and research cost as initial screening in selection of protein or isolates to be tested in vitro or in vivo.Methods: In this study, E6 and E7 gene sequences were obtained from 12 samples of  Indonesian isolates, which  were compared with HPV16R (prototype) and 6 standard isolates in the category of European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and North American (NA) branch from Genbank. Bioedit v.7.0.0 was used to analyze the composition and substitution of single amino acids. Phylogenetic analysis of E6 and E7 genes and proteins was performed using Clustal X (1.81) and NJPLOT softwares. Effects of single amino acid substitutions on protein function of E6 and E7 were analysed by SNAP.Results: Java variants and isolate ui66* belonged to European branch, while the others belonged to Asian and African branches. Twelve changes of amino acids were found in E6 and one in E7 proteins. SNAP analysis showed two non neutral mutations, i.e. R10I and C63G in E6 proteins. R10I mutations were found in Af-2 genotype (AF472509) and Indonesian isolates (Af2*), while C63G mutation was found only in Af2*.Conclusion: E6 proteins of HPV16 variants were more variable than E7. SNAP analysis showed that only E6 protein of African-2 branch had functional differences compared to HPV16R.

Photolabile Protecting Group‐Mediated Synthesis of 2‐Deoxy‐Glycosides

2021 ◽  
Author(s):  
Xiaoqian Li ◽  
Zhi Ma ◽  
Rongkun Liu ◽  
Mattan Hurevich ◽  
You Yang
Keyword(s):  
Protecting Group ◽  
Photolabile Protecting Group

Amino acid-templated zinc phosphites: low-dimensional structures, fluorescence, and nonlinear optical properties

2021 ◽  
Author(s):  
Yumei Mao ◽  
Xuehua Dong ◽  
Yuandan Deng ◽  
Jing Li ◽  
Ling Huang ◽  
...  
Keyword(s):  
Optical Properties ◽  
Amino Acid ◽  
Nonlinear Optical ◽  
Uv Light ◽  
Nonlinear Optical Properties ◽  
Light Irradiation ◽  
Blue Fluorescence ◽  
Structure Directing Agent ◽  
Uv Light Irradiation ◽  
Low Dimensional

Two new zinc phosphites were prepared using the amino acid alanine as structure-directing agent. They have tubular and ladder-like structures exhibiting blue fluorescence upon UV light irradiation. Notably, the tubular...

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