Discovery of highly active kynureninases for cancer immunotherapy through protein language model.

Tailor-made enzymes empower a wide range of versatile applications, although searching for the desirable enzymes often requires high throughput screening and thus poses significant challenges. In this study, we employed homology searches and protein language models to discover and prioritize enzymes by their kinetic parameters. We aimed to discover kynureninases as a potentially versatile therapeutic enzyme, which hydrolyses L-kynurenine, a potent immunosuppressive metabolite, to overcome the immunosuppressive tumor microenvironment in anticancer therapy.

Sea Fog Dissipation Prediction in Incheon Port and Haeundae Beach Using Machine Learning and Deep Learning.

Sea fog is a natural phenomenon that reduces the visibility of manned vehicles and vessels that rely on the visual interpretation of traffic. Fog clearance, also known as fog dissipation, is a relatively under-researched area when compared with fog prediction. In this work, we first analyzed meteorological observations that relate to fog dissipation in Incheon port (one of the most important ports for the South Korean economy) and Haeundae beach (the most populated and famous resort beach near Busan port).

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid-secretory phases.

Successful embryo implantation is the first step for establishing natural pregnancy and is dependent on the crosstalk between the embryo and a receptive endometrium. However, the molecular signaling events for successful embryo implantation are not entirely understood. To identify differentially expressed transcripts [long-noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs] and competing endogenous RNA (ceRNA) networks associated with endometrial receptivity, the current study analyzed gene expression profiles between proliferative and mid-secretory endometria in fertile women.

A Synthetic CPP33-Conjugated Active Domain Peptide Inhibits Invasion Ability of Non-Small Lung Cancer Cells.

Homeobox A9 () expression is associated with the aggressive growth of cancer cells and poor prognosis in lung cancer. Previously, we showed that can serve as a potential therapeutic target for the treatment of metastatic non-small cell lung cancer (NSCLC). In the present study, we have carried out additional studies toward the development of a peptide-based therapeutic agent.

Complete Genome of KY Using Flongle Provides Insight Into the Genetic Background of Optimal Adaption to Vaginal Econiche.

Despite the importance of and its unique characteristics for the study of vaginal adaption, its genome and genomic researches for identifying molecular backgrounds of these specific phenotypes are still limited. In this study, the first complete genome of was constructed using a cost-effective long-read sequencing platform, Flongle from Oxford Nanopore, and comparative genome analysis was conducted using a total of 1,046 strain genomes from 10 vaginal species. Single-molecule sequencing using Flongle effectively resolved the limitation of the 2nd generation sequencing technologies in dealing with genomic regions of high GC contents, and comparative genome analysis identified three potential core genes (INY, ZnuA, and ) of which was related to its specific adaption to the vaginal environment.

Decursinol from Angelica gigas Nakai enhances endometrial receptivity during implantation.

Background: Embryo implantation is essential for a successful pregnancy, and an elaborate synchronization between the receptive endometrium and trophoblast is required to achieve this implantation. To increase 'endometrial receptivity', the endometrium undergoes transformation processes including responses of adhesion molecules and cellular and molecular cell to cell communication. Many natural substances from traditional herbs have been studied to aid in the achievement of successful implantation.

Structural basis for recognition of Emi2 by Polo-like kinase 1 and development of peptidomimetics blocking oocyte maturation and fertilization.

In a mammalian oocyte, completion of meiosis is suspended until fertilization by a sperm, and the cell cycle is arrested by a biochemical activity called cytostatic factor (CSF). Emi2 is one of the CSFs, and it maintains the protein level of maturation promoting factor (MPF) by inhibiting ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Degradation of Emi2 via ubiquitin-mediated proteolysis after fertilization requires phosphorylation by Polo-like kinase 1 (Plk1).

22-S-Hydroxycholesterol protects against ethanol-induced liver injury by blocking the auto/paracrine activation of MCP-1 mediated by LXRα.

Chronic ethanol consumption causes hepatic steatosis and inflammation, which are associated with liver hypoxia. Monocyte chemoattractant protein-1 (MCP-1) is a hypoxia response factor that determines recruitment and activation of monocytes to the site of tissue injury. The level of MCP-1 is elevated in the serum and liver of patients with alcoholic liver disease (ALD); however, the molecular details regarding the regulation of MCP-1 expression are not yet understood completely.

A new class of peptidomimetics targeting the polo-box domain of Polo-like kinase 1.

Recent progress in the development of peptide-derived Polo-like kinase (Plk1) polo-box domain (PBD) inhibitors has led to the synthesis of multiple peptide ligands with high binding affinity and selectivity. However, few systematic analyses have been conducted to identify key Plk1 residues and characterize their interactions with potent Plk1 peptide inhibitors. We performed systematic deletion analysis using the most potent 4j peptide and studied N-terminal capping of the minimal peptide with diverse organic moieties, leading to the identification of the peptidomimetic 8 (AB-103) series with high binding affinity and selectivity.

Crystal structures of 26kDa Clonorchis sinensis glutathione S-transferase reveal zinc binding and putative metal binding.

The crystal structures of CsGST in two different space groups revealed that Asp26 and His79 coordinate a zinc ion. In one space group, His46 of an adjacent molecule participates in the coordination within 2.0Å.

Expression, purification, crystallization and preliminary X-ray analysis of the extracellular sensory domain of DraK histidine kinase from Streptomyces coelicolor.

The bacterium Streptomyces coelicolor produces useful antibiotics from its secondary metabolites. DraK is a sensory histidine kinase involved in the differential regulation of antibiotics in S. coelicolor through the DraR/DraK two-component system.

pH-dependent structural change of the extracellular sensor domain of the DraK histidine kinase from Streptomyces coelicolor.

Recently, the DraR/DraK (Sco3063/Sco3062) two-component system (TCS) of Streptomycescoelicolor has been reported to be involved in the differential regulation of antibiotic biosynthesis. However, it has not been shown that under which conditions and how the DraR/DraK TCS is activated to initiate the signal transduction process. Therefore, to understand the sensing mechanism, structural study of the sensory domain of DraK is highly required.

Expression, purification, crystallization and preliminary X-ray analysis of the human NORE1 SARAH domain.

NORE1 is an important tumour suppressor in human cancers that interacts with the pro-apoptotic protein kinase MST1/2 through SARAH domains. The SARAH domain (residues 366-413) of human NORE1 was expressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The crystal diffracted to 2.

Overexpression, purification, crystallization and preliminary X-ray crystallographic analysis of the periplasmic domain of outer membrane protein A from Acinetobacter baumannii.

Outer membrane protein A from Acinetobacter baumannii (AbOmpA) is a major outer membrane protein and a key player in the bacterial pathogenesis that induces host cell death. AbOmpA is presumed to consist of an N-terminal β-barrel transmembrane domain and a C-terminal periplasmic OmpA-like domain. In this study, the recombinant C-terminal periplasmic domain of AbOmpA was overexpressed in Escherichia coli, purified and crystallized using the vapour-diffusion method.

A histidine substitution confers metal binding affinity to a Schistosoma japonicum Glutathione S-transferase.

Glutathione S-transferases (GSTs) are multifunctional enzymes that are used as fusion tags on recombinant proteins in mammalian and Escherichia coli expression systems. We recently found that the Schistosoma japonicum GST (SjGST) displays weak Ni(2+) ion binding affinity. Glu26 and His79 were assumed to be its Ni(2+) binding sites based on the structure of the 26-kDa Clonorchis sinensis GST.

Structural snapshots of heparin depolymerization by heparin lyase I.

Heparin lyase I (heparinase I) specifically depolymerizes heparin, cleaving the glycosidic linkage next to iduronic acid. Here, we show the crystal structures of heparinase I from Bacteroides thetaiotaomicron at various stages of the reaction with heparin oligosaccharides before and just after cleavage and product disaccharide. The heparinase I structure is comprised of a beta-jellyroll domain harboring a long and deep substrate binding groove and an unusual thumb-resembling extension.

The presence of monoglucosylated N196-glycan is important for the structural stability of storage protein, arylphorin.

Although N-glycosylation has been known to increase the stability of glycoproteins, it is difficult to assess the structural importance of glycans in the stabilization of glycoproteins. APA (Antheraea pernyi arylphorin) is an insect hexamerin that has two N-glycosylations at Asn196 and Asn344 respectively. The glycosylation of Asn344 is critical for the folding process; however, glycosylation of Asn196 is not.

The target of RNAIII-activating protein (TRAP) from Staphylococcus aureus: purification, crystallization and preliminary X-ray analysis.

The target of the RNAIII-activating protein (TRAP) is a 21 kDa protein in which phosphorylation is activated by the RNAIII-activating protein (RAP), which causes an increase in RNAII and RNAIII synthesis and the production of the virulence factors. In an attempt to examine the structural role of TRAP in the signal transduction pathway, TRAP from Staphylococcus aureus was overexpressed, purified and crystallized using PEG 8000 and 5% Jeffamine M600 (pH 7.0), as precipitants by hanging-drop vapour diffusion methods at 287 K.

Crystallization and preliminary X-ray crystallographic study of UDP-glucose pyrophosphorylase (UGPase) from Helicobacter pylori.

UDP-glucose pyrophosphorylase (UGPase) catalyzes the synthesis of UDP-glucose, an essential metabolite in all living organisms. An X-ray crystallographic study of UGPase from Helicobacter pylori has been performed in order to elucidate its role in the regulation of this important metabolic pathway. UGPase was crystallized from 0.

Purification, crystallization and preliminary X-ray studies of ClpX from Helicobacter pylori.

ClpX, a member of the HSP (heat-shock protein) 100 family, functions as a molecular chaperone and is a regulatory subunit of the ClpXP protease. To understand the chaperone and regulatory mechanisms of ClpX, Helicobacter pylori ClpX has been overexpressed in Escherichia coli and crystallized at 295 K using (NH(4))(2)HPO(4) as precipitant. X-ray diffraction data have been collected to 2.