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1.
Polymers (Basel) ; 15(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36679178

RESUMO

Poly (methyl methacrylate) (PMMA) is a commonly used denture material with poor antimicrobial effects. This study investigated the antimicrobial effects of PMMA-containing silver-phosphate glass. We fabricated a novel material comprising PMMA-containing silver-phosphate glass. Then, microhardness, flexural strength, and gloss unit were analyzed. Antimicrobial activity against Streptococcus mutans and Candida albicans was investigated. Colony-forming units were counted, and antimicrobial rates were measured. Biocompatibility tests were performed using a colorimetric MTT assay for evaluating cell metabolic activity. The microhardness, flexural strength, and gloss unit of the experimental groups (with silver-phosphate glass) were not significantly different from those of the control group (no silver-phosphate glass) (P > 0.05), which showed clinically valid values. With increasing proportions of silver-phosphate glass, the antimicrobial activity against the two microorganisms increased (P < 0.05). Furthermore, S. mutans showed more than 50% antimicrobial activity in 4%, 6%, and 8% experimental groups, C. albicans showed more than 50% antimicrobial activity in 6% and 8% groups, and a statistically significant difference in antimicrobial activity was observed compared to the control (P < 0.05). The cell viability of the experimental groups was not significantly different from that of the control group (P > 0.05). Both control and experimental groups showed approximately 100% cell viability. These results suggest that silver-phosphate glass is a promising antimicrobial material in dentistry.

2.
Allergy Asthma Immunol Res ; 15(1): 19-31, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36693355

RESUMO

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

3.
Materials (Basel) ; 16(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36676418

RESUMO

Removal of 1,3-butadiene from cigarette smoke plays an important role in human health and environmental protection. Herein, a series of UiO-66 X% containing different ratios of the -NH2 group was synthesized via the solvothermal method by using terephthalic acid (H2BDC) and 2-aminoterephthalic acid (NH2-BDC) as ligands. Using GO as support, a series of UiO-66-NH2/GO Y% were prepared by controlling the ratio of UiO-66-NH2 and GO. The effects of -NH2 and GO contents on the structure and composition of MOFs were investigated. Finally, the different -NH2 contents of UiO-66 X% and the different GO contents of UiO-66-NH2/GO Y% were applied in 1,3-butadiene removal from cigarette smoke. The results showed that UiO-66 X% with the higher contents of -NH2 showed a higher rate of 1,3-butadiene removal, and UiO-66-NH2/GO Y% with the GO contents of 5% showed the highest removal rate of about 33.85%, which was 25.54% higher than that of activated carbon. In addition, the saturation capacity of the adsorbent materials for 1,3-butadiene was as high as 210.01-239.54 mg/g, showing great potential in reducing harmful components in cigarette smoke and environmental protection.

4.
Molecules ; 28(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36677934

RESUMO

Xanthomonas spp. are important plant pathogens that seriously endanger crop yields and food security. RpfF is a key enzyme that is involved in the synthesis of diffusible signal factor (DSF) signals and predominates in the signaling pathway regulating quorum sensing (QS) in Xanthomonas. Currently, novel RpfF enzyme-based quorum sensing agents have been proposed as a promising strategy for the development of new pesticides. However, few reports are available that comprehensively summarize the progress in this field. Therefore, we provide a comprehensive review of the recent advances in DSF-mediated QS and recently reported inhibitors that are proposed as bactericide candidates to target the RpfF enzyme and control plant bacterial diseases.


Assuntos
Xanthomonas , Percepção de Quorum , Proteínas de Bactérias/metabolismo , Transdução de Sinais
5.
J Ginseng Res ; 47(1): 133-143, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36644388

RESUMO

Background: Past studies suggested that ginseng extracts and ginseng-derived molecules exerted significant regulatory effects on skin. However, no reports have described the effects of ginseng-derived nanoparticles (GDNPs) on skin cell proliferation and wound healing. In this study, we investigated whether GDNPs regulate the proliferation of skin cells and promote wound healing in a mouse model. Methods: GDNPs were separated and purified via differential centrifugation and sucrose/D2O gradient ultracentrifugation. GDNP uptake, cell proliferation and cell cycle progression were measured by confocal microscopy, CCK-8 assay and flow cytometry, respectively. Cell migration and angiogenic effects were assessed by the wound scratch assay and tube formation assay, respectively. ELISA was used to detect extracellular matrix secretion. The relevant signaling pathway was confirmed by western blotting. The effects of GDNPs on skin wound healing were assessed by wound observation, HE staining, and western blotting. Results: GDNPs possessed the essential features of exosomes, and they were accumulated by skin cells. Treatment with GDNPs notably enhanced the proliferation of HaCaT, BJ and HUVECs. GDNPs also enhanced the migration in HaCaT cells and HUVECs and angiogenesis in HUVECs. GDNPs increased the secretion of MMP-1, fibronectin-1, elastin-1, and COL1A1 in all three cell lines. GDNPs regulated cell proliferation through the ERK and AKT/ mTOR pathways. Furthermore, GDNPs facilitated skin wound healing and decreased inflammation in a mouse skin wound model. Conclusion: GDNPs can promote skin wound healing through the ERK and AKT/mTOR pathways. GDNPs thus represent an alternative treatment for chronic skin wounds.

6.
Math Biosci Eng ; 20(1): 807-836, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650790

RESUMO

The application of a high-speed parallel manipulator necessitates the adoption of a lightweight design to reduce dead weight. However, this increases the elastic deformation of certain components, affecting the dynamic performance of the system. This study examined a 2-DOF planar flexible parallel manipulator. A dynamic model of the parallel manipulator composed of fully flexible links was established using a floating reference coordinate system and a combination of the finite element and augmented Lagrange multiplier methods. A dynamic analysis of the simplified model under three driving torque modes showed that the axial deformation was less than the transverse deformation by three orders of magnitude. Further, the kinematic and dynamic performance of the redundant drive was significantly better than that of the non-redundant drive, and the vibration was well suppressed in the redundant drive mode. In addition, the comprehensive performance of driving Mode 2 was better than that of the other two modes. Finally, the validity of the dynamic model was verified by modeling via Adams. The modular modeling method is conducive to the extension to other models and programming. Furthermore, the dynamic model of the established fully flexible link system can aid in optimizing the lightweight design and dynamic performance of the parallel manipulator.


Assuntos
Análise de Elementos Finitos , Desenho de Equipamento , Fenômenos Biomecânicos
7.
Artigo em Inglês | MEDLINE | ID: mdl-36656472

RESUMO

The present study used Chrysomya megacephala larvae (CML) to transform food waste into safe and high-quality fish feed to substitute fish meal as a source of protein for growing Oujiang color common carps followed by a human health risk assessment of polycyclic aromatic hydrocarbons (PAHs). The results showed the ∑PAH concentration in the CML fed with food waste ranged from 50 to 370 µg kg-1, and the most abundant PAH compound in the CML was BaP, contributing 59-84% of ∑PAHs. The Pearson correlation analysis results indicated no correlation between the ∑PAH concentrations and the culture substrate ratio (p > 0.05). Concentrations of BaP in the CML decreased with the increase of breeding density (p < 0.01). The residues as organic fertilizers have no potential ecological risk for PAHs. The biotransformed larva meal was used to partially or completely replace the fish meal as supplementary protein in the experimental feeds (T0, 0%; T50, 50%; T100, 100%). No significant difference (p < 0.05) of survival rate, lipid, and protein content in Oujiang color common carp was noted among T0, T50, and T100 fish feeds. Concentrations of ∑PAHs in Oujiang color common carp fed with the CML fish feeds all met the food safety standards in the European Union (EU). Furthermore, the consumption of Oujiang color common carps fed with the CML feed does not pose any health risks of PAHs for humans.

8.
Proc Natl Acad Sci U S A ; 120(2): e2208070120, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36598944

RESUMO

Secretory proteins are cotranslationally or posttranslationally translocated across lipid membranes via a protein-conducting channel named SecY in prokaryotes and Sec61 in eukaryotes. The vast majority of secretory proteins in bacteria are driven through the channel posttranslationally by SecA, a highly conserved ATPase. How a polypeptide chain is moved by SecA through the SecY channel is poorly understood. Here, we report electron cryomicroscopy structures of the active SecA-SecY translocon with a polypeptide substrate. The substrate is captured in different translocation states when clamped by SecA with different nucleotides. Upon binding of an ATP analog, SecA undergoes global conformational changes to push the polypeptide substrate toward the channel in a way similar to how the RecA-like helicases translocate their nucleic acid substrates. The movements of the polypeptide substrates in the SecA-SecY translocon share a similar structural basis to those in the ribosome-SecY complex during cotranslational translocation.


Assuntos
Proteínas de Bactérias , Proteínas de Escherichia coli , Proteínas SecA/metabolismo , Proteínas de Bactérias/metabolismo , Canais de Translocação SEC/metabolismo , Modelos Moleculares , Transporte Proteico , Peptídeos/metabolismo , Proteínas de Escherichia coli/metabolismo
9.
Gen Physiol Biophys ; 42(1): 1-12, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36705300

RESUMO

This study aimed to identify immune-based prognostic biomarkers associated with metastasis of osteosarcoma. Based on the GEO and TCGA databases, 437 differentially expressed genes were screened between primary and metastatic osteosarcoma. Weighted gene co-expression network analysis (WGCNA) revealed 496 genes in turquoise module which had the highest correlation with osteosarcoma metastasis. Within these two group genes, 122 common genes involved in osteosarcoma metastasis were identified. These genes were enriched in chemokine activity, chemokine receptor binding, TNF signaling pathway, etc. Survival analysis revealed 8 prognostic genes (ANK3, EGR1, FBP1, FOS, KIFC3, MAOB, ISLR and MFAP4) from the 122 genes. RT-qPCR showed that all of these eight genes were differentially expressed between 143B and MNNG/HOS Cl cells. Various infiltrating immune cells showed significant differences between primary and metastatic osteosarcoma. Expression of all the 8 prognostic genes was correlated with infiltration abundance of multiple immune cells, such as follicular helper T cells, activated dendritic cells. In addition, 10 microRNAs and 7 transcription factors that targeted these prognostic genes were predicted. In conclusion, 8 immune-based prognostic genes associated with osteosarcoma metastasis were identified.


Assuntos
MicroRNAs , Osteossarcoma , Humanos , Prognóstico , MicroRNAs/metabolismo , Biomarcadores , Perfilação da Expressão Gênica , Osteossarcoma/genética , Osteossarcoma/patologia , Proteínas de Transporte/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Cinesinas/genética , Cinesinas/metabolismo
10.
Aquat Toxicol ; 255: 106373, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36630844

RESUMO

Hypoxia and Cu2+ pollution often occur simultaneously in aquatic ecosystems and jointly affect physiology of fish. As the respiratory and ion exchange tissue of fish, how gill responds to the stress induced by these two abiotic environmental factors is still unclear. We have conducted a study by exposing largemouth bass (Micropterus salmoides) to hypoxia (2.0 mg·L-1) and/or Cu2+ (0.5 mg·L-1) for 28 days to answer this question. We subsequently studied respiratory rate, Cu2+ transport, endoplasmic reticulum (ER) stress, mitochondrial damage, and morphology in gill tissue on day 7, 14, 21 and 28. We found that hypoxia exposure increased the respiratory rate of largemouth bass, reflecting the response of largemouth bass to cope with hypoxia. Of note, Cu2+ entered gill by specifically binding to CTR1 and its accumulation dramatically in gill disrupted the response of largemouth bass to hypoxia. Hypoxia and/or Cu2+ exposure led to ER stress and mitochondrial damage in gills of largemouth bass. ER stress and mitochondrial damage induced apoptosis by activating caspase-8 and caspase-9 signaling pathways, respectively. Apoptosis induced by hypoxia and Cu2+ exposure had a positive and synergistic effect on gill remodeling by reducing interlamellar cell masses. In addition, Cu2+ exposure induced hypoxia-like remodeling to gill morphology through mechanisms similar to hypoxia exposure. Most of gene expression changed mainly within 21 days and recovered to the control level on day 28, reflecting the acclimation of largemouth bass to hypoxia and/or Cu2+ exposure at gene expression level. Overall, our research suggests that chronic hypoxia and Cu2+ exposure could induce gill remodeling of largemouth bass through ER stress, mitochondrial damage and apoptosis. The outcomes could provide an insight for fish environmental adaptation and environmental toxicology.


Assuntos
Bass , Poluentes Químicos da Água , Animais , Bass/metabolismo , Brânquias , Ecossistema , Poluentes Químicos da Água/toxicidade , Hipóxia/metabolismo , Apoptose , Estresse do Retículo Endoplasmático
11.
Exp Ther Med ; 25(1): 4, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36561627

RESUMO

The present study describes the clinical profile and ankyrin 1 (ANK1) mutation status of a Chinese family with hereditary spherocytosis (HS). A young male patient (proband) was diagnosed with HS after presenting with anaemia and jaundice. The Coombs test was negative and spherocytes were found in peripheral blood smears. Magnetic resonance imaging showed splenomegaly and splenic iron depositions. The red blood cell osmotic fragility test was positive. The eosin-5'-maleimide binding test showed reduced mean channel fluorescence. Whole-exome sequencing revealed a novel ANK1 mutation (c.4707G>A), resulting in a nonsense mutation (p.Trp1569*). The patient's father, paternal aunt and paternal grandmother exhibited comparable clinical symptoms and Sanger sequencing confirmed the same mutation in these family members. To the best of our knowledge, an HS pedigree with this novel ANK1 nonsense mutation has not been previously reported. At the same time, the unique clinical presentation of this pedigree helps our understanding of the heterogeneity of clinical manifestations of HS.

13.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22283000

RESUMO

The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 400,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using antibody pools. (ii) we mapped the antibody response at the individual level using blood from strigently curated vaccine and convalescent cohorts. In pooled antibody samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases we observed increased antibody breadth to variants that were yet to be in circulation. Resolution of viral neutralisation at the cohort level supported equivalent coverage across prior and emerging variants with emerging isolates BQ.1.1, XBB.1 and BR.2.1 the most evasive. Further, these emerging variants were resistant to Evusheld, whilst neutralization resistance to Sotrovimab was restricted to BQ.1.1 and further supported by lack of Spike glycoprotein binding to this variant. An outgrowth advantage through better utilization of TMPRSS2 was observed across BQ lineages and not those derived from BA.2.75. We conclude at this current point in time that variants derived from BQ lineages can evade antibodies at levels equivalent to their most evasive BA.2.75 counterparts but sustain an entry phenotype that would promote an additional outgrowth advantage.

14.
Animals (Basel) ; 12(23)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36496933

RESUMO

To understand the characteristics of the fish community structure and biomass particle-size spectrum in the upper reaches of the Jinsha River, fish and environmental surveys were conducted in 21 segments of the upper reaches of the Jinsha River in September 2019 and June 2020. A total of 4062 fish belonging to 2 orders, 5 families, 18 genera, and 28 species were collected. Among them, Cyprinidae fish were the most abundant (14 species), accounting for 50.00%. The Shannon index and Pielou evenness index values varied from 0.402-1.770 and 0.254-0.680, respectively. The dominant species of fish were Triplophysa stenura, Schizothorax wangchiachii, and Schizopygopsis malacanthus. Redundancy analysis (RDA) was used to analyse the relationship between the fish community and environmental factors. Velocity, altitude, and dissolved oxygen were the main influencing factors of fish community structure differences in the upper reaches of the Jinsha River. The abundance/biomass curves showed that the fish communities in the upper reaches of the Jinsha River were moderately or severely disturbed. The standardized biomass particle-size spectrum of fish showed that the degree of disturbance of fish in tributaries was much lower than that in the main stream. Compared with the historical data, the fish community structure in the Jinsha River has changed significantly, with the number of exotic species increasing, and the individual fish showing miniaturization and younger ages. It is suggested that habitat conservation strategies be adopted in the upper tributaries of the Jinsha River to provide a reference for the restoration of fishery resources and the conservation of fish diversity in the Yangtze River.

15.
Cancers (Basel) ; 14(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36497289

RESUMO

(1) Background: Early diagnosis and treatment are essential to reduce the mortality rate of bladder cancer (BLCA). We aimed to develop deep learning (DL)-based weakly supervised models for the diagnosis of BLCA and prediction of overall survival (OS) in muscle-invasive bladder cancer (MIBC) patients using whole slide digitized histological images (WSIs). (2) Methods: Diagnostic and prognostic models were developed using 926 WSIs of 412 BLCA patients from The Cancer Genome Atlas cohort. We collected 250 WSIs of 150 BLCA patients from the Renmin Hospital of Wuhan University cohort for external validation of the models. Two DL models were developed: a BLCA diagnostic model (named BlcaMIL) and an MIBC prognostic model (named MibcMLP). (3) Results: The BlcaMIL model identified BLCA with accuracy 0.987 in the external validation set, comparable to that of expert uropathologists and outperforming a junior pathologist. The C-index values for the MibcMLP model on the internal and external validation sets were 0.631 and 0.622, respectively. The risk score predicted by MibcMLP was a strong predictor independent of existing clinical or histopathologic indicators, as demonstrated by univariate Cox (HR = 2.390, p < 0.0001) and multivariate Cox (HR = 2.414, p < 0.0001) analyses. The interpretability of DL models can help in the analysis of critical regions associated with tumors to enrich the information obtained from WSIs. Furthermore, the expression of six genes (ANAPC7, MAPKAPK5, COX19, LINC01106, AL161431.1 and MYO16-AS1) was significantly associated with MibcMLP-predicted risk scores, revealing possible potential biological correlations. (4) Conclusions: Our study developed DL models for accurately diagnosing BLCA and predicting OS in MIBC patients, which will help promote the precise pathological diagnosis of BLCA and risk stratification of MIBC to improve clinical treatment decisions.

16.
J Clin Med ; 11(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36498655

RESUMO

(1) Purpose: Although assessment of tumor-infiltrating lymphocytes (TILs) has been acknowledged to have important predictive prognostic value in muscle-invasive bladder cancer (MIBC), it is limited by inter- and intra-observer variability, hampering widespread clinical application. We aimed to evaluate the prognostic value of quantitative TILs score based on a machine learning (ML) algorithm to identify MIBC patients who might benefit from immunotherapy or the de-escalation of therapy. (2) Methods: We constructed an artificial neural network classifier for tumor cells, lymphocytes, stromal cells, and "ignore" cells from hematoxylin-and-eosin-stained slide images using the QuPath open source software. We defined four unique TILs variables based on ML to analyze TILs measurements. Pathological slide images from 133 MIBC patients were retrospectively collected as the discovery set to determine the optimal association of ML-read TILs variables with patient survival outcomes. For validation, we evaluated an independent external validation set consisting of 247 MIBC patients. (3) Results: We found that all four TILs variables had significant prognostic associations with survival outcomes in MIBC patients (p < 0.001 for all comparisons), with higher TILs score being associated with better prognosis. Univariate and multivariate Cox regression analyses demonstrated that electronic TILs (eTILs) variables were independently associated with overall survival after adjustment for clinicopathological factors including age, sex, and pathological stage (p < 0.001 for all analyses). Results analyzed in different subgroups showed that the eTILs variable was a strong prognostic factor that was not redundant with pre-existing clinicopathological features (p < 0.05 for all analyses). (4) Conclusion: ML-driven cell classifier-defined TILs variables were robust and independent prognostic factors in two independent cohorts of MIBC patients. eTILs have the potential to identify a subset of high-risk stage II or stage III-IV MIBC patients who might benefit from adjuvant immunotherapy.

17.
Mitochondrial DNA B Resour ; 7(12): 2044-2047, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506786

RESUMO

Wallacea dactyliferae Maulik 1919 (Coleoptera: Chrysomelidae) has been reported as a new invasive palm pest in Asia recently. So far, a total of 29 species have been reported in Wallacea. In the present study, the whole mitochondrial genome of W. dactyliferae was identified for the first time (also for the first species of Wallacea) by using high throughput sequencing systems. The entire genome is 16,243 bp in length (ACCN: OK513040) consisting of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and an A + T-rich region. Phylogenetic analysis revealed that insects from the same subfamily were clustered together, with W. dactyliferae being clustered together with other Cassidinae species. This study can provide essential DNA molecular data for further phylogenetic and evolutionary analyses for Chrysomelidae family of the Coleoptera order.

19.
Cell Rep ; 41(13): 111864, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36577382

RESUMO

During heart maturation, gap junctions assemble into hemichannels and polarize to the intercalated disc at cell borders to mediate electrical impulse conduction. However, the molecular mechanism underpinning cardiac gap junction assembly remains elusive. Herein, we demonstrate an important role for the deubiquitinating enzyme cylindromatosis (CYLD) in this process. Depletion of CYLD in mice impairs the formation of cardiac gap junctions, accelerates cardiac fibrosis, and increases heart failure. Mechanistically, CYLD interacts with plakoglobin and removes lysine 63-linked polyubiquitin chains from plakoglobin. The deubiquitination of plakoglobin enhances its interaction with the desmoplakin/end-binding protein 1 complex localized at the microtubule plus end, thereby promoting microtubule-dependent transport of connexin 43 (Cx43), a key component of gap junctions, to the cell membrane. These findings establish CYLD as a critical player in regulating gap junction assembly and have important implications in heart development and diseases.


Assuntos
Conexina 43 , Coração , Animais , Camundongos , Conexina 43/genética , gama Catenina/metabolismo , Miocárdio/metabolismo , Junções Comunicantes/metabolismo , Enzima Desubiquitinante CYLD/metabolismo
20.
Chem Catal ; 2(10): 2658-2674, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36569427

RESUMO

Flavin-dependent halogenases (FDHs) catalyze selective halogenation of electron-rich aromatic compounds without the need for harsh oxidants required by conventional oxidative halogenation reactions. Predictive models for halogenase site selectivity could greatly improve their utility for chemical synthesis. Toward this end, we analyzed the structures and selectivity of three halogenase variants evolved to halogenate tryptamine with orthogonal selectivity. Crystal structures and reversion mutations revealed key residues involved in altering halogenase selectivity. Density functional theory calculations and molecular dynamics simulations are both consistent with hypohalous acid as the active halogenating species in FDH catalysis. This model was used to accurately predict the site selectivity of halogenase variants toward different synthetic substrates, providing a valuable tool for implementing halogenases in biocatalysis efforts.

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