Biology subjects

Yin, J.

Publications and source records attributed to Yin, J..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

A noncanonical glycoprotein H complex enhances cytomegalovirus entry

Human cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the incomplete understanding of the diverse protein complexes the virus uses to infect cells. In Herpesviridae, the gH/gL glycoprotein heterodimer is expected to be a basal element of virion cell entry machinery. For HCMV, gH/gL forms a "trimer" with gO and a "pentamer" with UL128, UL130, and UL131A, with each complex binding distinct receptors to enter varied cell types. Here, we reveal a third glycoprotein complex, abundant in HCMV virions, which significantly enhances infection of endothelial cells. In this "3-mer" complex, gH, without gL, associates with UL116 and UL141, an immunoevasin previously known to function in an intracellular role. Cryo-EM reveals the virion-surface 3-mer is structurally unique among Herpesviridae gH complexes, with gH-only scaffolding, UL141-mediated dimerization and a heavily glycosylated UL116 cap. Given that antibodies directed at gH and UL141 each can restrict HCMV replication, our work highlights this virion surface complex as a new target for vaccines and antiviral therapies.

microbiology↗

bioRxiv2024

Steerable Tape-Spring Needle for Autonomous Sharp Turns Through Tissue

Steerable needles offer a minimally invasive method to deliver treatment to hard-to-reach tissue regions. We introduce a new class of tape-spring steerable needles capable of sharp turns ranging from 15 to 150 degrees with a turn radius as low as 3mm, which minimizes surrounding tissue damage. In this work, we derive and experimentally validate a geometric model for our steerable needle design. We evaluate both manual and robotic steering of the needle along a Dubins path in 7 kPa and 13 kPa tissue phantoms, simulating our target clinical application in healthy and unhealthy liver tissue. We conduct experiments to measure needle robustness to stiffness transitions between non-homogeneous tissues. We demonstrate progress towards clinical use with needle tip tracking via ultrasound imaging, navigation around anatomical obstacles, and integration with a robotic autonomous steering system.

bioengineering↗

bioRxiv2024

Engineering a Cell-Based Orthogonal Ubiquitin Transfer Cascade for Profiling the Substrates of RBR E3 Parkin

The E3 ubiquitin (UB) ligase Parkin utilizes a Ring-Between-Ring (RBR) domain to mediate the transfer of UB to its substrates to regulate diverse cellular functions, including mitochondrial quality control, cell cycle progression, metabolism programming, and the establishment of synaptic functions. Mutations affecting the E3 ligase activity of Parkin are associated with cancer and Parkinsons disease (PD). An essential role of Parkin is to synthesize UB chains on the surface of damaged mitochondria to initiate mitophagy. Still, it is not clear how Parkin carries out other biological functions through the ubiquitination of its downstream targets in the cell. We hypothesized that a comprehensive substrate profile of Parkin would facilitate the discovery of ubiquitination pathways underpinning its multifaceted roles in cell regulation and reveal mechanistic linkages between Parkin malfunction and disease development. Here, we used phage display to assemble an orthogonal ubiquitin transfer (OUT) cascade of Parkin that can exclusively deliver an engineered UB mutant (xUB) to Parkin and its substrates in living cells. We then generated a substrate profile of Parkin by purifying xUB-conjugated proteins from cells and identifying them by proteomics. The OUT screen identified Parkin substrates involved in DNA replication, protein translation, intracellular protein transport, and rhythmic regulation. Based on previous literature implicating alterations in membrane vesicle trafficking in PD, we verified Parkin-catalyzed ubiquitination of Rab GTPases (Rab1a, Rab5a, Rab5c, Rab7a, Rab8a, Rab10, an Rab13) as well as CDK5, with reconstituted ubiquitination reactions in vitro and in cells. We also found chemical-induced stimulation of mitophagy enhanced Parkin-mediated ubiquitination of Rab proteins. These findings demonstrate that the OUT cascade of Parkin can serve as an empowering tool for identifying Parkin substrates to elucidate its cellular functions.

biochemistry↗

bioRxiv2024

Successive pattern in winter wheat main stem structure modeling

1.With the rise of research on functional structural plant models (FSPMs), it is particularly important to realistically describe the structural traits of a plant. In 3D FSPMs, the true structural information of the canopy can make the models estimation of functional traits more accurate. Since canopy is the medium of the crop stands that sense and respond to the external environment, accurate estimation of detailed organ sizes in crop canopy is crucial, and current FSPMs still need to be improved. Here the structure of wheat (Triticum aestivum) was measured in detail at the phytomer level. Dataset was built which covers a set of [~]100 cultivars and 11 site-year under various field managements such as sowing density, inter-row, nitrogen fertilizer and sowing date. The relationships of successive phytomer sizes were quantified and the variance was analyzed for each independent experiment, only site was found as a significant impact factor. A conceptual model based on the successive pattern was proposed and validated for detailed final phytomer sizes. Then we coupled the meteorology data - the ratio of average daily gross radiation and temperature during the emergence and architecture mature with the model. The validation has taken place three times to emphasize models independent of cultivars, sites dependent and the ability of model parameters deriving from environmental factors, respectively. The results revealed the feasibility of the newly built wheat main stem structure model with the R2 higher than 0.85. Compared with ADEL-Wheat and Sirius Quality, the model achieved better performance in blade width and blade area estimation. According to the concise and easily acquired parameters of this model, it has potential for high throughput phenotyping detail wheat canopy structure. Previous work on the relationship between blade width and circumference of apex shoot in maize illustrated that the cell number was the most likely explanation for this pattern, which means the same work holds for similar crops.

developmental biology↗

bioRxiv2024

Synergically enhanced anti-tumor immunity of in vivo CAR by circRNA vaccine boosting

Chimeric Antigen Receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies. However, it is limited to individualized cell therapy and faces challenges, including high costs, extended preparation time, and limited efficacy against solid tumors. Here, we generated circular RNAs (circRNAs) encoding Chimeric Antigen Receptor (CAR) transmembrane proteins, referred to as circRNACAR, which mediated remarkable tumor killing in both T cells and macrophages. In addition, macrophages exhibited efficient phagocytosis of tumor cells and pro-inflammatory polarization induced by circRNACAR in vitro. We demonstrated that circRNACAR, delivered with immunocyte-tropic lipid nanoparticles (LNPs), significantly inhibited tumor growth, improved survival rates and induced a pro-inflammatory tumor microenvironment in mice. Importantly, the combination of circRNAAnti-HER2-CAR and circRNA-based cancer vaccines encoding the corresponding transmembrane HER2 antigen, termed circRNAHER2, exhibited synergistically enhanced anti-tumor activity. This proof-of-concept study demonstrated that the combination of circRNA-based in vivo CAR and vaccines, termed in vivo CAR-VAC, holds the potential to become an upgraded off-the-shelf immunotherapy.

immunology↗

bioRxiv2024

OsAAI1-OsMADS25 module orchestrates root morphogenesis by fine-tuning IAA in drought stressed rice

Indole-3-acetic acid (IAA) plays a critical role as a plant hormone in regulating the growth and development of the root system in plants, particularly in enhancing their ability to withstand abiotic stress. In this study, we found that overexpression of OsAAI1 promoted the growth of rice root system. The length of primary root, the number of lateral roots, the density of lateral roots, and the number of adventitious roots of overexpression of OsAAI1 (OE19) were significantly better than those of the wild type (ZH11) and the mutant line (osaai1), and the IAA content of OE19 was significantly higher than those of ZH11 and osaai1. We also found that exogenous application of IAA could compensate for the root growth defect caused by the osaai1 mutation. OE19 had the highest number and widest distribution of total roots under the water-cut drought treatment, and exogenous application of IAA attenuated the growth inhibitory effect of drought stress on osaai1. Our study also revealed that OsAAI1 interacts with the MADS-box family transcription factor OsMASD25. Additionally, the application of IAA helped alleviate the growth inhibitory effects of drought stress on osmads25.Importantly, OsMADS25 interaction with OsAAI1 was found to enhance the transcriptional expression of its downstream target genes LAX1 and OsBAG4, which are crucial genes in rices response to drought stress. These findings suggest that OsAAI1 and OsMADS25 are crucial in rices drought acclimation process by regulating downstream gene expression and influencing the IAA signaling pathway. Author summaryThe root system is a crucial organ for crop plants as it facilitates the absorption of water and nutrients, contributing to their drought resistance. Indole-3-acetic acid (IAA) plays a pivotal role in the growth of various types of roots in plants. Under drought stress conditions, changes in IAA levels and transport can impact the morphology of plant roots. This research illustrates that OsAAI1 positively influences rice root development and enhances the plants response to drought stress through the auxin signaling pathway. The study reveals a physical interaction between OsAAI1 and the transcription factor OsMADS25. This interaction boosts the expression of the auxin synthesis gene OsYUC4 and suppresses the auxin inhibitory factor OsIAA14, thereby promoting the auxin signaling pathway, stimulating rice root growth, and enhancing the plants ability to withstand drought. Furthermore, the interaction between OsAAI1 and OsMADS25 has been found to also positively affect the expression of the genes LAX1 and OsBAG4, which is associated with activated drought resistance in rice plants.

plant biology↗

bioRxiv2024

Pharmacodynamic modeling of colistin and imipenem against in vitro Pseudomonas aeruginosa biofilms

IntroductionAntibiotic treatment of chronic biofilm-associated infections can be challenging. Characterization of pharmacokinetic-pharmacodynamic (PK-PD) relationships for biofilm-associated infections may be relevant to inform the design of antibiotic treatment regimens for biofilm-associated infections. To this end, we aim to develop a mathematical PK-PD model for planktonic and biofilm bacterial infections and demonstrate how PK-PD simulations can be used to design optimized dosing schedules, using imipenem and colistin as proof-of-concept examples. MethodsPharmacodynamic models were developed using time-kill assay data from planktonic and alginate-bead biofilm cultures of Pseudomonas aeruginosa exposed to imipenem or colistin. The PD models were coupled to population PK models for plasma and epithelial lining fluid (ELF) to translate PD relationships for clinical dosing schedules and PK-PD indices. ResultsThe developed models incorporated sensitive and resistant bacterial subpopulations and were able to adequately capture the observed time-kill data. Simulation studies identified differences in suppression of bacterial growth dynamics for multiple clinical intravenous and inhalation-based treatment regimens and were used to infer biofilm-specific PK-PD indices associated with ELF target site concentrations. ConclusionIn conclusion, we demonstrate the utility of mathematical modeling for the characterization of PK-PD relationships underlying time-kill kinetic profiles in biofilm-associated infections and their utility in translating experimental findings to inform the optimization of clinical dosing schedules.

pharmacology and toxicology↗

bioRxiv2024

Contraction-induced endocardial id2b plays a dual role in regulating myocardial contractility and valve formation

Biomechanical cues play an essential role in sculpting organ formation. Comprehending how cardiac cells perceive and respond to biomechanical forces is a biological process with significant medical implications that remains poorly understood. Here we show that biomechanical forces activate endocardial id2b (inhibitor of DNA binding 2b) expression, thereby promoting cardiac contractility and valve formation. Taking advantage of the unique strengths of zebrafish, particularly the viability of embryos lacking heartbeats, we systematically compared the transcriptomes of hearts with impaired contractility to those of control hearts. This comparison identified id2b as a gene sensitive to blood flow. By generating a knockin reporter line, our results unveiled the presence of id2b in the endocardium, and its expression is sensitive to both pharmacological and genetic perturbations of contraction. Furthermore, id2b loss-of-function resulted in progressive heart malformation and early lethality. Combining RNA-seq analysis, electrophysiology, calcium imaging, and echocardiography, we discovered profound impairment in atrioventricular (AV) valve formation and defective excitation-contraction coupling in id2b mutants. Mechanistically, deletion of id2b reduced AV endocardial cell proliferation and led to a progressive increase in retrograde blood flow. In the myocardium, id2b directly interacted with the bHLH component tcf3b (transcription factor 3b) to restrict its activity. Inactivating id2b unleashed its inhibition on tcf3b, resulted in enhanced repressor activity of tcf3b, which subsequently suppressed the expression of nrg1 (neuregulin 1), an essential mitogen for heart development. Overall, our findings identify id2b as an endocardial cell-specific, biomechanical signaling-sensitive gene, which mediates intercellular communications between endocardium and myocardium to sculpt heart morphogenesis and function.

developmental biology↗

bioRxiv2024

Multi-omics Reveals Immune Response and Metabolic Profiles during High-Altitude Mountaineering

The physiological perturbations induced by high-altitude exposure in mountain climbers, manifesting as metabolic and immunologic deviations, have been previously reported but are not fully understood. In this study, we obtained longitudinal multi-omic profiles of blood samples for healthy mountain climbers during two mountaineering stages (acclimatization and extreme altitude mountaineering). Our integrative assay included metabolomics and lipidomics profiling of plasma coupled with single-cell transcriptomic analysis of 375,722 immune cells. Longitudinal analysis revealed dynamic immune response profiles, during the acclimatization period, characterized by the downregulation of inflammatory responses in monocytes and classical dendritic cells (cDCs) and an increase in the proportion of cytotoxic CD8+ T cells with enhanced immune effector processes. In contrast, during extreme altitude mountaineering, the activation of inflammatory responses and impairment of T cell effector function were observed, concomitant with an increased cellular response to hypoxia and oxidative stress pathways. Furthermore, we found upregulated glycolysis and antioxidant gene expression during extreme altitude mountaineering, which was primarily orchestrated by HIF1A and NFE2L2, while decreased expression of these genes was observed in dysregulated plasmacytoid dendritic cells (pDCs). Finally, high-resolution plasma metabolic analysis revealed significant alterations in the metabolism of climbers, involving enhanced glutamine and fatty acid metabolism.

bioinformatics↗

bioRxiv2024

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

developmental biology↗

bioRxiv2024

Uncovering disease-related multicellular pathway modules on large-scale single-cell transcriptomes with scPAFA

Pathway analysis is a crucial analytical phase in disease research on single-cell RNA sequencing (scRNA-seq) data, offering biological interpretations based on prior knowledge. However, currently available tools for generating cell-level pathway activity scores (PAS) exhibit computational inefficacy in large-scale scRNA-seq datasets. Besides, disease-related pathways are commonly identified by cross-condition comparisons in each cell type, neglecting the potential multicellular patterns. Here, we present single-cell pathway activity factor analysis (scPAFA), a Python library designed for large-scale single-cell dataset allowing rapid PAS computation and uncovering biologically interpretable disease-related multicellular pathway modules, which are low-dimensional representations of disease-related PAS variance in multiple cell types. Application on colorectal cancer (CRC) dataset with 371,223 cells and large-scale lupus atlas over 1.2 million cells demonstrated that scPAFA can achieve > 33-fold decreases in runtime of PAS computation and further identified reliable and interpretable multicellular pathway modules that capture the transcriptomic features of CRC tumor status and transcriptional abnormalities in lupus patients, respectively.

bioinformatics↗

bioRxiv2024

Click-free imaging of carbohydrate trafficking in live cells using an azido photothermal probe

Real-time tracking of intracellular carbohydrates remains challenging. While click chemistry allows bio-orthogonal tagging with fluorescent probes, the reaction permanently alters the target molecule and only allows a single snapshot. Here, we demonstrate click-free mid-infrared photothermal (MIP) imaging of azide-tagged carbohydrates in live cells. Leveraging the micromolar detection sensitivity for 6-azido-trehalose (TreAz) and the 300-nm spatial resolution of MIP imaging, the trehalose recycling pathway in single mycobacteria, from cytoplasmic uptake to membrane localization, is directly visualized. A peak shift of azide in MIP spectrum further uncovers interactions between TreAz and intracellular protein. MIP mapping of unreacted azide after click reaction reveals click chemistry heterogeneity within a bacterium. Broader applications of azido photothermal probes to visualize the initial steps of the Leloir pathway in yeasts and the newly synthesized glycans in mammalian cells are demonstrated.

cell biology↗

bioRxiv2024

Unraveling the gut microbiota of Tibetan chickens: insights into highland adaptation and ecological advantages

Tibetan animals have several unique advantages owing to the harsh ecological conditions under which they live. Tibetan mammals have been studied extensively. However, understanding of the advantages and underlying mechanisms of the representative high-latitude bird, the Tibetan chicken (Gallus gallus, TC), remains limited. The gut microbiota of animals has been conclusively shown to be closely related to both host health and host environmental adaptation. This study aimed to explore the relationships between the cecal microbiome and the advantages of TCs based on comparisons among three populations: native TCs residing on the plateau, domestic TCs living in the plain, and one native plain species. Metatranscriptomic sequencing revealed a significant enrichment of active Bacteroidetes but a loss of active Firmicutes in native TCs. Additionally, the upregulated expression of genes in the cecal microbiome of native TCs showed enriched pathways related to energy metabolism, glycan metabolism, and the immune response. Furthermore, the expression of genes involved in the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) was upregulated in the cecal microbiome of native TCs. Data from targeted metabolomics further confirmed elevated levels of certain SCFAs and SBAs in the cecum of native TCs. Based on the multi-omics association analysis, we proposed that the higher ratio of active Bacteroidetes/Firmicutes may be attributed to the efficient energy metabolism and stronger immunological activity of native TCs. Our findings provide a better understanding of the interactions between gut microbiota and highland adaptation, and novel insights into the mechanisms by which Tibetan chickens adapt to the plateau hypoxic environment. IMPORTANCEThe composition and function of the active cecal microbiome were significantly different between the plateau Tibetan chicken population and the plain chicken population. Higher expression genes related to energy metabolism and immune response were found in the cecal microbiome of the plateau Tibetan chicken population. The cecal microbiome in the plateau Tibetan chicken population exhibited higher biosynthesis of short-chain fatty and secondary bile acids, resulting in higher cecal content of these metabolites. The active Bacteroidetes/Firmicutes ratio in the cecal microbiome may contribute to the high-altitude adaptive advantage of the plateau Tibetan chicken population.

microbiology↗

bioRxiv2024

YamOmics: A comprehensive data resource on yam multi-omics

Yams (Dioscorea spp.) are a highly important class of horticultural crops, serving as a staple food for millions of people in Africa and contributing significantly to food security. They are also widely cultivated in East Asia as medicinal herbs, bringing substantial economic incomes. Diverse omics data play a pivotal role in advancing yam research and breeding. However, these data are often scattered, lacking in systematic organization and analysis, which underscores the need for centralized and comprehensive data management. In view of this, we gathered extensive omics data and developed the Yam Omics Database (YamOmics; https://biotec.njau.edu.cn/yamdb). The database currently offers a vast and diverse range of omics data, covering genomic, transcriptomic and plastomic data from 41 distinct yam species, along with detailed records of genomic variants from [~]1000 germplasms, and gene expression profiles from [~]200 samples. Additionally, the database features thorough annotations, encompassing aspects like genome synteny, ortholog groups, signaling pathways, gene families and protein interactions. To support yam basic biology and breeding research, it is also equipped with a suite of user-friendly online tools, including PCR primer design, CRISPR design, expression analysis, enrichment analysis, and kinship analysis tools.

plant biology↗

bioRxiv2023

Engineered Bacillus subtilis as oral probiotics to target circulating lactic acid

Elevated lactate concentrations are implicated in various acute and chronic diseases such as sepsis and mitochondrial dysfunction, respectively. Conversely, ineffective lactate clearance is associated with poor clinical prognoses and high mortality in these diseases. While several groups have proposed using small molecule inhibitors and enzyme replacement to reduce circulating lactate, there are few practical and effective ways to manage this condition. Recent evidence suggests that lactate is exchanged between systemic circulation and the gut, allowing bidirectional modulation between the gut microbiota and peripheral tissues. Inspired by these findings, this work seeks to engineer spore-forming probiotic B. subtilis strains to enable intestinal delivery of lactate oxidase as a therapeutic enzyme. After strain optimization, we showed that oral administration of engineered B. subtilis spores to the gut of mice reduced elevations in blood lactate in two different mouse models involving exogenous challenge or pharmacologic perturbation without disrupting gut microbiota composition, liver function, or immune homeostasis. Taken together, through the oral delivery of engineered probiotic spores to the gastrointestinal tract, our proof-of-concept study offers a practical strategy to aid in the management of disease states with elevated blood lactate and provides a new approach to knocking down circulating metabolites to help understand their roles in host physiological and pathological processes. Significance StatementThis study pioneers the use of engineered Bacillus subtilis spores as an oral probiotic therapy to enhance the clearance of elevated blood lactate, a condition linked to severe health issues like sepsis and metabolic disorders. By genetically modifying these spores to deliver therapeutic enzymes directly to the gut, we demonstrated a practical, effective method to modulate systemic lactate levels. This approach leverages the natural exchange between the gut microbiota and systemic circulation, offering a new strategy for managing diseases associated with lactate dysregulation. The safety and efficacy of this method were validated in mouse models, providing a foundation for future clinical applications.

bioengineering↗

bioRxiv2023

Study on the preparation of bovine milk exosomes and the stability of lyophilized powder

Bovune milk exosomes (MK-exo) have bioactive effects on the health of consumers and can also serve as excellent drug delivery vehicles. However, long-term preservation and transportation remain major challenges at present. In this report, high-quality MK-exo are prepared on a large scale. We then developed a lyophilization method belonging to MK-exo, and performed acceleration and long-term stability experiments on the lyophilized MK-exo to evaluate the effect of lyophilization. The results showed that the lyophilized MK-exo can be stored at room temperature for at least 3 months and 2-8{degrees}C for 15 months. These findings provide data support for further understanding of the properties and applications of MK-exo.

bioengineering↗

bioRxiv2023

The E3 ubiquitin ligase RNF216 contains a linear ubiquitin chain-determining-like domain that functions to regulate dendritic arborization and dendritic spine type in hippocampal neurons

Of the hundreds of E3 ligases found in the human genome, the RING-between RING (RBR) E3 ligase in the LUBAC (linear ubiquitin chain assembly complex) complex HOIP (HOIL-1-interacting protein or RNF31), contains a unique domain called LDD (linear ubiquitin chain determining domain). HOIP is the only E3 ligase known to form linear ubiquitin chains, which regulate inflammatory responses and cell death via activation of the NF-{kappa}B pathway. We identified an amino acid sequence within the RNF216 E3 ligase that shares homology to the LDD domain found in HOIP (R2-C). Here, we show that the R2-C domain of RNF216 promotes self-assembly of all ubiquitin chains, with a dominance for those assembled via K63-linkages. Deletion of the R2-C domain altered RNF216 localization, reduced dendritic complexity and changed the distribution of apical dendritic spine morphology types in primary hippocampal neurons. These changes were independent of the RNF216 RBR catalytic activity as expression of a catalytic inactive version of RNF216 had no effect. These data show that the R2-C domain of RNF216 diverges in ubiquitin assembly function from the LDD of HOIP and and functions independently of RNF216 catalytic activity to regulate dendrite development in neurons.

neuroscience↗

bioRxiv2023

Understanding structural and functional diversity of ATP-PPases using protein domains and functional families in CATH database

ATP-Pyrophosphatases (ATP-PPases) are the most primordial lineage of the large and diverse HUP (HIGH-motif proteins, Universal Stress Proteins, ATP-Pyrophosphatase) superfamily. There are four different ATP-PPase substrate-specificity groups, and members of each group show considerable sequence variation across the domains of life despite sharing the same catalytic function. Over the past decade, there has been a >20-fold expansion in the number of ATP-PPase domain structures most recently from advances in protein structure prediction (e.g. Alphafold2). Using the enriched structural information, we have characterised the two most populated ATP-PPase substrate-specificity groups, the NAD-synthases (NAD) and GMP synthases (GMPS). We performed local structural and sequence comparisons between the NADS and GMPS from different domains of life and identified taxonomic-group specific structural functional motifs. As GMPS and NADS are potential drug targets of pathogenic microorganisms including Mycobacterium tuberculosis, structural motifs specific to bacterial GMPS and NADS provide new insights that may aid antibacterial-drug design.

bioinformatics↗