Jianshu Dong

Red fluorescent protein mRuby is an important labelling tool for super-resolution imaging. With the addition of thioacetate, it was found here that the red colour of the protein aqueous solution changed, although still clear and transparent. Light spectrophotometry exhibited that, with the increase of thioacetate concentration, the absorption spectra changed abruptly. Crystallography showed the binding of thioacetate at the chromophore of mRuby. Atomic-resolution serial structures of mRuby single crystal showed snapshots of step-by-step reduction of thioacetate upon light irradiation. This observation suggests new insights for FP-compound interaction research and light energy harvesting for green chemistry.

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Anthraquinone hits outperform l -arginine on E. coli ArgRS. The Asp118–Asp317 electrostatic clamp is the dominant hotspot. DFT/MESP and per-residue energetics give an SAR blueprint for rapid, cost-effective antibacterial design.

Fluorescent proteins are capable of photoinduced electron transfer, and this property has vast application potentials for chemistry, green catalysis, sustainable energy supply, etc. However, the detailed mechanism, the boundaries, and the maximum possible output reduction potentials remain elusive. Herein, three different metal ions of various reduction potentials are applied to examine their interaction with fluorescent protein PsmOrange through X‐ray crystallography and spectrometry. PsmOrange is an irreversible photo‐switchable fluorescent protein that's easily oxidized, causing obvious alterations including cleavage of peptide chain, red‐shift of fluorescence, and color change. It's shown here that electron transfer from the chromophore to bound metal ions leads to quenching of fluorescence, which causes neither redox damage to the chromophore, nor breakage of peptide chain, nor red‐shift of fluorescence, as suggested by structures and spectrophotometry. The perseverant nature of fluorescent proteins promises limitless possibilities to exploit. The reducing power decreases as the distance from the chromophore increases, setting up natural boundaries for the utilization of electrons transferred from fluorescent proteins. The mechanism uncovered here has profound implications for the employment of fluorescent proteins for practical application purposes.

HOXA1 is a member of the HOX gene family, encoding a DNA-binding transcription factor that regulates gene expression, morphogenesis, cell proliferation, and differentiation. It plays a crucial role in the normal development of the human head, nervous system, heart, and brain vascular system. Numerous studies have shown that dysregulation of HOXA1 is associated with developmental abnormalities, various human diseases, and cancer. In this review, we summarize the role of the HOXA1 gene in different cancers. Additionally, we delve into the regulatory mechanisms of HOXA1 in carcinogenesis and tumor progression, upstream and downstream target genes, and pathway regulation. Finally, we emphasize its potential as a target for cancer diagnosis and treatment, proposing strategies for targeting HOXA1, related non-coding proteins, and the HOXA1/PBX dimer in cancer therapy.

As one of the key processes of photosynthesis, carbon fixation and reduction is one of the most important biochemical reactions on planet Earth. Yet, reducing oxidized carbon elements through directly harnessing solar energy by using water-soluble, simple enzymes continues to be challenging. Here, CO₂ and bicarbonate were found to be transformed into methanol by fluorescent protein mRuby by using light as the single energy input. The binding of substrates to mRuby chromophore was supported by crystallography and light spectrometry. Gas chromatography showed the generation of methanol in mRuby-bicarbonate aqueous solution upon sunlight illumination. Atomic-resolution serial structures of mRuby showed snapshots of the step-by-step reduction of bicarbonate and CO₂. The amino, imino, or carboxylate group of residues near the chromophore was within hydrogen bonding distances of the substrates, respectively. A decrease in fluorescence was observed upon binding of bicarbonate, and the energy liberated from fluorescence was presumably utilized for methanol production. This research represents an exciting example of sunlight-driven photobiocatalysis by water-soluble small proteins. The new, green, and sustainable mechanisms uncovered here indicated great promises to harness solar energy straightforwardly, for, i.e., fuel production and green chemistry.

F-box proteins are involved in multiple cellular processes through ubiquitylation and consequent degradation of targeted substrates. Any significant mutation in F-box protein-mediated proteolysis can cause human malformations. The various cellular processes F-box proteins involved include cell proliferation, apoptosis, invasion, angiogenesis, and metastasis. To target F-box proteins and their associated signaling pathways for cancer treatment, researchers have developed thousands of F-box inhibitors. The most advanced inhibitor of FBW7, NVD-BK M120, is a powerful P13 kinase inhibitor that has been proven to bring about apoptosis in cancerous human lung cells by disrupting levels of the protein known as MCL1. Moreover, F-box Inhibitors have demonstrated their efficacy for treating certain cancers through targeting particular mutated proteins. This paper explores the key studies on how F-box proteins act and their contribution to malignancy development, which fabricates an in-depth perception of inhibitors targeting the F-box proteins and their signaling pathways that eventually isolate the most promising approach to anti-cancer treatments.

83 Structures of human nNOS, 55 structures of human eNOS, 13 structures of iNOS, and about 126 reported NOS-bound compounds are summarized and analyzed. Structural and statistical analysis show that, at least one copy of each analyzed compound binds to the active site (the substrate arginine binding site) of human NOS. And binding features of the three isoforms show differences, but the binding preference of compounds is not in the way helpful for inhibitor design targeting nNOS and iNOS, or for activator design targeting eNOS. This research shows that there is a strong structural and functional similarity between oxygenase domains of human NOS isoforms, especially the architecture, residue composition, size, shape, and distribution profile of hydrophobicity, polarity and charge of the active site. The selectivity and efficacy of inhibitors over the rest of isoforms rely a lot on chance and randomness. Further increase of selectivity via rational improvement is uncertain, unpredictable and unreliable, therefore, to achieve high selectivity through targeting this site is complicated and requires combinative investigation. After analysis on the current two targeting sites in NOS, the highly conserved arginine binding pocket and H4B binding pocket, new potential drug-targeting sites are proposed based on structure and sequence profiling. This comprehensive analysis on the structure and interaction profiles of human NOS and bound compounds provides fresh insights for drug discovery and pharmacological research, and the new discovery here is practically applied to guide protein-structure based drug discovery.