BioChem

2 pages, 288 KiB

Open AccessEditorial

BioChem: A New International and Interdisciplinary Journal

by Buyong Ma

BioChem 2021, 1(1), 49-50; https://doi.org/10.3390/biochem1010005 - 18 Jun 2021

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The advances of biological science have fundamentally changed our world and our understanding of human beings [...] Full article

13 pages, 10280 KiB

Open AccessArticle

De Novo Drug Design Using Artificial Intelligence Applied on SARS-CoV-2 Viral Proteins ASYNT-GAN

by Ivan Jacobs and Manolis Maragoudakis

BioChem 2021, 1(1), 36-48; https://doi.org/10.3390/biochem1010004 - 05 Apr 2021

Cited by 7 | Viewed by 5376

Abstract

Computer-assisted de novo design of natural product mimetics offers a viable strategy to reduce synthetic efforts and obtain natural-product-inspired bioactive small molecules, but suffers from several limitations. Deep learning techniques can help address these shortcomings. We propose the generation of synthetic molecule structures that optimizes the binding affinity to a target. To achieve this, we leverage important advancements in deep learning. Our approach generalizes to systems beyond the source system and achieves the generation of complete structures that optimize the binding to a target unseen during training. Translating the input sub-systems into the latent space permits the ability to search for similar structures, and the sampling from the latent space for generation. Full article

(This article belongs to the Special Issue Computational Analysis of Proteomes and Genomes)

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10 pages, 2023 KiB

Open AccessFeature PaperArticle

Nucleoredoxin Downregulation Reduces β-Catenin Levels and Shifts Hematopoietic Differentiation towards Myeloid Lineage In Vitro

by Alejandro Pérez-Fernández, Guillermo López-Ruano, Rodrigo Prieto-Bermejo, Carmen Sánchez-Bernal, Jesús Sánchez-Yagüe and Ángel Hernández-Hernández

BioChem 2021, 1(1), 26-35; https://doi.org/10.3390/biochem1010003 - 04 Apr 2021

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Abstract

The importance of dissecting signaling pathways governing cell differentiation is based on their relevance not only for understanding basic biological phenomena but also for better comprehending the underlying mechanisms of pathologic alterations such as cancer. A paradigm of cell differentiation processes is hematopoiesis, where a single stem cell gives rise to multiple, fully differentiated, cell lineages. Nucleoredoxin (Nrx), a member of the thioredoxin family, is an important redox-sensitive modulator of Wnt/β-catenin signaling, a key pathway for the control of hematopoiesis. In this work, the relevance of Nrx for the differentiation of mouse hematopoietic progenitor cells has been analyzed in vitro. Nrx silencing leads to a dramatic reduction in the size of the Lin⁻ and LSK progenitor populations. Moreover, there is also a remarkable decrease in CD3⁺ cells and an enhancement in the percentage of CD11b⁺Gr1⁻ myeloid cells. This myeloid bias would agree with the inhibition of the Wnt/β-catenin pathway. Interestingly, a reduction in β-catenin at the protein level was observed upon Nrx silencing. Our results strongly support the importance of Nrx for hematopoietic differentiation, which could be mediated by the regulation of the Wnt/β-catenin pathway. Full article

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7 pages, 1866 KiB

Open AccessFeature PaperArticle

The Hsp60 Protein of Helicobacter Pylori Exhibits Chaperone and ATPase Activities at Elevated Temperatures

by Jose A. Mendoza, Julian L. Ignacio and Christopher M. Buckley

BioChem 2021, 1(1), 19-25; https://doi.org/10.3390/biochem1010002 - 03 Apr 2021

Cited by 2 | Viewed by 2829

Abstract

The heat-shock protein, Hsp60, is one of the most abundant proteins in Helicobacter pylori. Given its sequence homology to the Escherichia coli Hsp60 or GroEL, Hsp60 from H. pylori would be expected to function as a molecular chaperone in this organism. H. pylori is a type of bacteria that grows on the gastric epithelium, where the pH can fluctuate between neutral and 4.5, and the intracellular pH can be as low as 5.0. We previously showed that Hsp60 functions as a chaperone under acidic conditions. However, no reports have been made on the ability of Hsp60 to function as a molecular chaperone under other stressful conditions, such as heat stress or elevated temperatures. We report here that Hsp60 could suppress the heat-induced aggregation of the enzymes rhodanese, malate dehydrogenase, citrate synthase, and lactate dehydrogenase. Moreover, Hsp60 was found to have a potassium and magnesium-dependent ATPase activity that was stimulated at elevated temperatures. Although, Hsp60 was found to bind GTP, the hydrolysis of this nucleotide could not be observed. Our results show that Hsp60 from H. pylori can function as a molecular chaperone under conditions of heat stress. Full article

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18 pages, 11313 KiB

Open AccessArticle

A Novel FACS-Based Workflow for Simultaneous Assessment of RedOx Status, Cellular Phenotype, and Mitochondrial Genome Stability

by Patrick M. McTernan, Paige S. Katz, Constance Porretta, David A. Welsh and Robert W. Siggins

BioChem 2021, 1(1), 1-18; https://doi.org/10.3390/biochem1010001 - 02 Apr 2021

Viewed by 2815

Abstract

Intracellular reduction-oxidation (RedOx) status mediates a myriad of critical biological processes. Importantly, RedOx status regulates the differentiation of hematopoietic stem and progenitor cells (HSPCs), mesenchymal stromal cells (MSCs) and maturation of CD8+ T Lymphocytes. In most cells, mitochondria are the greatest contributors of intracellular reactive oxygen species (ROS). Excess ROS leads to mitochondrial DNA (mtDNA) damage and protein depletion. We have developed a fluorescence-activated cell sorting (FACS)-based protocol to simultaneously analyze RedOx status and mtDNA integrity. This simultaneous analysis includes measurements of ROS (reduced glutathione (GSH)), ATP5H (nuclear encoded protein), MTCO1 (mitochondrial DNA encoded protein), and cell surface markers to allow discrimination of different cell populations. Using the ratio of MTCO1 to ATP5H median fluorescence intensity (MFI), we can gain an understanding of mtDNA genomic stability, since MTCO1 levels are decreased when mtDNA becomes significantly damaged. Furthermore, this workflow can be optimized for sorting cells, using any of the above parameters, allowing for downstream quantification of mtDNA genome copies/nucleus by quantitative PCR (qPCR). This unique methodology can be used to enhance analyses of the impacts of pharmacological interventions, as well as physiological and pathophysiological processes on RedOx status along with mitochondrial dynamics in most cell types. Full article

(This article belongs to the Special Issue Computational Analysis of Proteomes and Genomes)

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BioChem, Volume 1, Issue 1 (June 2021) – 5 articles

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