Current Protein and Peptide Science - Volume 23, Issue 4, 2022

S-adenosylhomocysteine nucleosidase (MTAN) is a protein that plays a crucial role in several pathways of bacteria that are essential for its survival and pathogenesis. In addition to the role of MTAN in methyl-transfer reactions, methionine biosynthesis, and polyamine synthesis, MTAN is also involved in bacterial quorum sensing (QS). In QS, chemical signaling autoinducer (AI) secreted by bacteria assists cell to cell communication and is regulated in a cell density-dependent manner. They play a significant role in the formation of bacterial biofilm. MTAN plays a major role in the synthesis of these autoinducers. Signaling molecules secreted by bacteria, i.e., AI-1 are recognized as acylated homoserine lactones (AHL) that function as signaling molecules within bacteria. QS enables bacteria to establish physical interactions leading to biofilm formation. The formation of biofilm is a primary reason for the development of multidrug-resistant properties in pathogenic bacteria like Enterococcus faecalis (E. faecalis). In this regard, inhibition of E. faecalis MTAN (EfMTAN) will block the QS and alter the bacterial biofilm formation. In addition to this, it will also block methionine biosynthesis and many other critical metabolic processes. It should also be noted that inhibition of EfMTAN will not have any effect on human beings as this enzyme is not present in humans. This review provides a comprehensive overview of the structural-functional relationship of MTAN. We have also highlighted the current status, enigmas that warrant further studies, and the prospects for identifying potential inhibitors of EfMTAN for the treatment of E. faecalis infections. In addition to this, we have also reported structural studies of EfMTAN using homology modeling and highlighted the putative binding sites of the protein.

Despite antimicrobial resistance, which is attributed to the misuse of broad-spectrum antibiotics, antibiotics can indiscriminately kill pathogenic and beneficial microorganisms. These events disrupt the delicate microbial balance in both humans and animals, leading to secondary infections and other negative effects. Antimicrobial peptides (AMPs) are functional natural biopolymers in plants and animals. Due to their excellent antimicrobial activities and absence of microbial resistance, AMPs have attracted enormous research attention. We reviewed the antibacterial, antifungal, antiviral, antiparasitic, as well as antitumor properties of AMPs and research progress on AMPs. In addition, we highlighted various recommendations and potential research areas for their progress and challenges in practical applications.

Enterococcus faecalis (E. faecalis) is an opportunistic multidrug-resistant (MDR) pathogen found in the guts of humans and farmed animals. Due to the occurrence of (MDR) strain there is an urgent need to look for an alternative treatment approach. E. faecalis is a Gram-positive bacterium, which is among the most prevalent multidrug resistant hospital pathogens. Its ability to develop quorum sensing (QS) mediated biofilm formation further exacerbates the pathogenicity and triggers lifethreatening infections. Therefore, developing a suitable remedy for curing E. faecalis mediated enterococcal infections is an arduous task. Several putative virulence factors and proteins are involved in the development of biofilms in E. faecalis. Such proteins often play important roles in virulence, disease, and colonization by pathogens. The elucidation of the structure-function relationship of such protein drug targets and the interacting compounds could provide an attractive paradigm towards developing structure-based drugs against E. faecalis. This review provides a comprehensive overview of the current status, enigmas that warrant further studies, and the prospects toward alleviating the antibiotic resistance in E. faecalis. Specifically, the role of biofilm and quorum sensing (QS) in the emergence of MDR strains had been elaborated along with the importance of the protein drug targets involved in both the processes.

Sickle cell disease (SCD) is an autosomal recessive trait of genetic hemoglobin disorder whose prevalence is varied from 5 to 25 % of the world population. It is characterized by the presence of hemoglobin (HbS) instead of normal hemoglobin (HbA). An individual suffering from sickle cell disease is likely to be at risk of osteonecrosis, which is a form of ischemic bone infarction which causes intolerable degenerative joint problems and can affect 30-50% of people with sickle cell disease. The femoral head is the most frequent epiphyseal location in osteonecrosis with sickle cell disease. In this review, the Bone morphogenetic protein (BMP)-a subfamily of transforming growth factor-β (TGF-β) characteristics outlined the osteoblastogenesis potentiality via using combinatorial or advanced treatment approaches. In this review, we aim to describe the Bone morphogenetic proteins' role in Skeleton diseases and discuss the potent osteogenic BMPs (majorly BMP-2, BMP-6, and BMP-7) with therapeutic benefits.

Human parasites cause several diseased conditions with high morbidity and mortality in a large section of the population residing in various geographical areas. Nearly three billion people suffer from either one or many parasitic infections globally, with almost one million deaths annually. In spite of extensive research and advancement in the medical field, no effective vaccine is available against prominent human parasitic diseases that necessitate identification of novel targets for designing specific inhibitors. Vitamin B6 is an important ubiquitous co-enzyme that participates in several biological processes and plays an important role in scavenging ROS (reactive oxygen species) along with providing resistance to oxidative stress. Moreover, the absence of the de novo vitamin B6 biosynthetic pathway in human parasites makes this pathway indispensable for the survival of these pathogens. Pyridoxal kinase (PdxK) is a crucial enzyme for vitamin B6 salvage pathway and participates in the process of vitamers B6 phosphorylation. Since the parasites are dependent on pyridoxal kinase for their survival and infectivity to the respective hosts, it is considered a promising candidate for drug discovery. The detailed structural analysis of PdxK from disease-causing parasites has provided insights into the catalytic mechanism of this enzyme as well as significant differences from their human counterpart. Simultaneously, structure-based studies have identified small lead molecules that can be exploited for drug discovery against protozoan parasites. The present review provides structural and functional highlights of pyridoxal kinase for its implication in developing novel and potent therapeutics to combat fatal parasitic diseases.

Aims: The main goal of the Russian part of C-HPP is to detect and functionally annotate missing proteins (PE2-PE4) encoded by human chromosome 18. To achieve this goal, it is necessary to use the most sensitive methods of analysis. Background: However, identifying such proteins in a complex biological mixture using mass spectrometry (MS)-based methods is difficult due to the insufficient sensitivity of proteomic analysis methods. A possible solution to the problem is the pre-fractionation of a complex biological sample at the sample preparation stage. Objective: This study aims to measure the detection limit of SRM SIS analysis using a standard set of UPS1 proteins and find a way to enhance the sensitivity of the analysis and to, detect proteins encoded by the human chromosome 18 in liver tissue samples, and compare the data with transcriptomic analysis of the same samples. Methods: Mass spectrometry, data-dependent acquisition, selected reaction monitoring, highperformance liquid chromatography, data-dependent acquisition in combination with pre-fractionation by alkaline reversed-phase chromatography, selected reaction monitoring in combination with prefractionation by alkaline reversed-phase chromatography methods were used in this study. Results: The results revealed that 100% of UPS1 proteins in a mixture could only be identified at a concentration of at least 10^-9 Ц#156;. The decrease in concentration leads to protein losses associated with technology sensitivity, and no UPS1 protein is detected at a concentration of 10^-13 Ц#156;. Therefore, the two-dimensional fractionation of samples was applied to improve sensitivity. The human liver tissue was examined by selected reaction monitoring and shotgun methods of MS analysis using onedimensional and two-dimensional fractionation to identify the proteins encoded by human chromosome 18. A total of 134 proteins were identified. The overlap between proteomic and transcriptomic data in human liver tissue was ~50%. Conclusion: The sample concentration technique is well suited for a standard UPS1 system that is not contaminated with a complex biological sample. However, it is not suitable for use with a complex biological protein mixture. Thus, it is necessary to develop more sophisticated fractionation systems for the detection of all low-copy proteins. This weak convergence is due to the low sensitivity of proteomic technology compared to transcriptomic approaches. Also, total mRNA was used to perform RNA-seq analysis, but not all detected mRNA molecules could be translated into proteins. This introduces additional uncertainty in the data; in the future, we plan to study only translated mRNA molecules-the translatome. Data is available via ProteomeXchange with identifier PXD026997.