Christian, N. | bioRxiv Science

bioRxiv2021

A Molecular Docking Study Of Human STEAP2 For The Discovery Of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates

Prostate cancer refers to uncontrolled abnormal cell growth (Cancer) within the prostate gland. The disease is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa being 5.2% and many of the diagnosed patients are found to have advanced stage prostate cancer. This study aimed to use STEAP2 protein (prostate cancer specific biomarker) for the discovery of new lead compounds against prostate cancer. To determine the most likely compound that can bind to STEAP2 protein, we docked the modelled STEAP2 3 Dimension structure against 2466 FDA (Food and Drug Administration) approved drug candidates using Autodock vina. Protein Basic Local Alignment Search Tool (BLASTp) search, Multiple Sequence Alignment (MSA), and phylogenetics were further carried out to analyse the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified of which Triptorelin had the highest binding energy (-12.1 kcal/mol). Leuprolide was the second most promising candidate with a docking energy of -11.2 kcal/mol. All the top 3 of 6 drugs interacted with highly conserved residues Ser-372 and Gly-369 in close proximity with the iron binding domain that was shown to be important for catalysis of metal reduction. The two drugs had earlier been approved for treatment of advanced prostate cancer but with an elusive mode of action. Thanks to this study we now have an insight on how their interaction with STEAP2 might be important during treatment. Author summaryPrevious studies on prostate cancer prevalence have shown that Uganda among other low to middle income countries has a high prostate cancer incidence rate. Majority of the patients at the time of diagnosis have advanced stage disease. While there has been great improvement in therapeutic options for prostate cancer over the last decade, the drugs currently used are still limited and not 100% effective making cure elusive. This is further compounded by undesirable side-effects from some of the treatments. Altogether this creates a need for the discovery of novel, safe, and efficacious chemotherapeutic agents with minimal or no side effects. In this study, we used a prostate cancer specific protein biomarker; STEAP2 that is highly expressed at all disease stages and is androgen independent and FDA approved drugs from the drugbank to help improve drug specificity, efficacy, and reduce undesirable side effects through in-silico methods. The results from the study give an insight on mechanisms of action of current therapy for advanced disease and suggest these very drugs be used even at early stage disease.

cancer biology↗

bioRxiv2021

Elevated CO2 reduces a common soybean leaf endophyte

Free-air CO2 enrichment (FACE) experiments have elucidated how climate change affects plant physiology and production. However, we lack a predictive understanding of how climate change alters interactions between plants and endophytes, critical microbial mediators of plant physiology and ecology. We leveraged the SoyFACE facility to examine how elevated [CO2] affected soybean (Glycine max) leaf endophyte communities in the field. Endophyte community composition changed under elevated [CO2], including a decrease in the abundance of a common endophyte, Methylobacterium sp. Moreover, Methylobacterium abundance was negatively correlated with co-occurring fungal endophytes. We then assessed how Methylobacterium affected the growth of co-occurring endophytic fungi in vitro. Methylobacterium antagonized most co-occurring fungal endophytes in vitro, particularly when it was more established in culture before fungal introduction. Variation in fungal response to Methylobacterium within a single fungal operational taxonomic unit (OTU) was comparable to inter-OTU variation. Finally, fungi isolated from elevated vs. ambient [CO2] plots differed in colony growth and response to Methylobacterium, suggesting that increasing [CO2] may affect fungal traits and interactions within the microbiome. By combining in situ and in vitro studies, we show that elevated [CO2] decreases the abundance of a common bacterial endophyte that interacts strongly with co-occurring fungal endophytes. We suggest that endophyte responses to global climate change will have important but largely unexplored implications for both agricultural and natural systems.

ecology↗