scholarly journals Genes Involved in Formation and Attachment of a Two-Carbon Chain as a Component of Eurekanate, a Branched-Chain Sugar Moiety of Avilamycin A

2005 ◽  
Vol 71 (1) ◽  
pp. 400-406 ◽  
Author(s):  
Irina Treede ◽  
Gerd Hauser ◽  
Agnes M�hlenweg ◽  
Carsten Hofmann ◽  
Maraike Schmidt ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Ribosomal Subunit ◽  
Carbon Chain ◽  
Biosynthetic Gene Cluster ◽  
Bacterial Protein ◽  
Structure Modification ◽  
Experimental Proof ◽  
Branched Chain ◽  
Bacterial Protein Synthesis

ABSTRACT Eurekanate belongs to the important class of branched-chain carbohydrates present in a wide variety of natural sources. It is a component of avilamycin A, a potent inhibitor of bacterial protein synthesis targeting the 50S ribosomal subunit. The present work provides experimental proof for the function of two genes of the avilamycin biosynthetic gene cluster, aviB1 and aviO2, that are both involved in avilamycin structure modification. The functions of both genes were identified by gene inactivation experiments and nuclear magnetic resonance analyses of extracts produced by the mutants. We suggest that both AviO2 and AviB1 are involved in the biosynthesis of eurekanate within avilamycin biosynthesis. Moreover, two other genes (aviO1 and aviO3) have been inactivated, resulting in a breakdown of avilamycin production in the mutants ITO1 and ITO3, which clearly shows the essential role of both enzymes in avilamycin biosynthesis. The exact functions of both aviO1 and aviO3 remained unknown.

scholarly journals Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Eldar Yagmurov ◽  
Darya Tsibulskaya ◽  
Alexey Livenskyi ◽  
Marina Serebryakova ◽  
Yury I. Wolf ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protein Synthesis ◽  
Antibiotic Resistance ◽  
Potent Inhibitor ◽  
Trna Synthetase ◽  
Bacterial Protein ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
Bacterial Protein Synthesis ◽  
Related Compounds

ABSTRACT The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like compounds by hydrolyzing the phosphoramide bond in toxic aspartamide-adenosine, rendering them inactive. IMPORTANCE Uncovering the mechanisms of resistance is a required step for countering the looming antibiotic resistance crisis. In this communication, we show how universally conserved histidine-triad hydrolases provide resistance to microcin C, a potent inhibitor of bacterial protein synthesis.

scholarly journals Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

2020 ◽  
Author(s):  
Eldar Yagmurov ◽  
Darya Tsibulskaya ◽  
Alexey Livenskyi ◽  
Marina Serebryakova ◽  
Yury I. Wolf ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protein Synthesis ◽  
Antibiotic Resistance ◽  
Potent Inhibitor ◽  
Trna Synthetase ◽  
Trojan Horse ◽  
Bacterial Protein ◽  
Mechanisms Of Resistance ◽  
Bacterial Protein Synthesis ◽  
Related Compounds

ABSTRACTThe Escherichia coli microcin C (McC) and related compounds are potent Trojan-horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by non-specific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This non-hydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside of the producing cells, special mechanisms evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by stand-alone genes confer resistance to McC–like compounds by hydrolyzing the phosphoramide bond in toxic aspartamide-adenosine, rendering them inactive.IMPORTANCEUncovering the mechanisms of resistance is a required step for countering the looming antibiotic resistance crisis. In this communication, we show how universally conserved histidine triad hydrolases provide resistance to microcin C – a potent inhibitor of bacterial protein synthesis.

Impact of Azithromycin and 8-Hydroxychloroquine in 2019 Novel Coronavirus (COVID-19) Pandemic: A Systematic Review

2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Srikanta Chandra ◽  
Preeta Bose ◽  
Jyoti Saxena ◽  
Muniraj Bhattacharya ◽  
Arun dutta ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Bacterial Protein ◽  
Lysosomal Ph ◽  
Inflammatory Conditions ◽  
Corona Virus ◽  
Novel Coronavirus ◽  
Antigen Presenting ◽  
Bacterial Protein Synthesis ◽  
Modern Era

As we know novel coronavirus is an emergent nuisance in this stipulated period. Corona virus is a group of enveloped viruses, with non-segmented, single stranded & positive sense RNA genomes. Human Corona virus is mainly subdivided into four categories such as 229E, NL63, OC43, HKU1. Epidemiologically it has a greater prevalence in the modern era. The features encountered in the clinical course of the disease are multifarious spanning from cough, sneezing, fever, breathlessness. It may take 2-14 days for a person to notice symptoms after infection. Azithromycin and 8 Hydroxychloroquine both plays an instrumental role for management of COVID-19. Azithromycin is a macrolide antibiotic and it binds with a 50s ribosome then inhibits bacterial protein synthesis. On the other hand 8-Hydroxychloroquine was approved by United State in the year of 1955 .Basically it is used as a antimalarial drugs . Briefly, in inflammatory conditions it binds with toll like receptor & blocks them. 8- hydroxychloroquine increases lysosomal pH in antigen presenting cells . In inflammatory conditions it blocks toll like receptors on plasmacytoid dendritic cells. In our review we focused on the role of Azithromycin, and 8-hydroxychloroquine in Covid-19 .

Tridegin, a Novel Peptidic Inhibitor of Factor XIIIa from the Leech, Haementeria ghilianii, Enhances Fibrinolysis In Vitro

1997 ◽  
Vol 77 (05) ◽  
pp. 0959-0963 ◽  
Author(s):  
Lisa Seale ◽  
Sarah Finney ◽  
Roy T Sawyer ◽  
Robert B Wallis
Keyword(s):  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Factor Xiiia ◽  
Cross Linking ◽  
Fibrinolytic Enzymes ◽  
Small Polypeptide ◽  
Tissue Plasminogen ◽  
Protein Cross Linking

SummaryTridegin is a potent inhibitor of factor Xllla from the leech, Haementeria ghilianii, which inhibits protein cross-linking. It modifies plasmin-mediated fibrin degradation as shown by the absence of D-dimer and approximately halves the time for fibrinolysis. Plasma clots formed in the presence of Tridegin lyse more rapidly when either streptokinase, tissue plasminogen activator or hementin is added 2 h after clot formation. The effect of Tridegin is markedly increased if clots are formed from platelet-rich plasma. Platelet-rich plasma clots are lysed much more slowly by the fibrinolytic enzymes used and if Tridegin is present, the rate of lysis returns almost to that of platelet- free clots. These studies indicate the important role of platelets in conferring resistance to commonly used fibrinolytic enzymes and suggest that protein cross-linking is an important step in this effect. Moreover they indicate that Tridegin, a small polypeptide, may have potential as an adjunct to thrombolytic therapy.

On the role of Zr substitution in structure modification and photoluminescence of Li5+2xLa3(Ta1−xZrx)2O12:Eu garnet phosphors

2021 ◽  
Author(s):  
Panpan Du ◽  
Siyuan Li ◽  
Xuejiao Wang ◽  
Qi Zhu ◽  
Ji-Guang Li
Keyword(s):  
Structure Modification

The role of Zr substitution in structure modification for a series of garnet-type Li5+2xLa3(Ta1−xZrx)2O12:Eu phosphors was identified, with which the observed luminescence behaviors of Eu3+ were successfully deciphered.

scholarly journals Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hauke S. Hillen ◽  
Elena Lavdovskaia ◽  
Franziska Nadler ◽  
Elisa Hanitsch ◽  
Andreas Linden ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Structural Basis ◽  
Peptidyl Transferase ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Ribosome ◽  
In Vitro Reconstitution

AbstractRibosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

scholarly journals The role of gut microbiota and amino metabolism in the effects of improvement of islet β-cell function after modified jejunoileal bypass

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cai Tan ◽  
Zhihua Zheng ◽  
Xiaogang Wan ◽  
Jiaqing Cao ◽  
Ran Wei ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Cell Function ◽  
Body Weight Gain ◽  
Fasting Blood Glucose ◽  
Jejunoileal Bypass ◽  
Β Cell ◽  
Β Cell Function ◽  
Branched Chain

AbstractThe change in gut microbiota is an important mechanism of the amelioration of type 2 diabetes mellitus (T2DM) after bariatric surgery. Here, we observe that the modified jejunoileal bypass effectively decreases body weight gain, fasting blood glucose, and lipids level in serum; additionally, islet β-cell function, glucose tolerance, and insulin resistance were markedly ameliorated. The hypoglycemic effect and the improvement in islet β-cell function depend on the changes in gut microbiota structure. modified jejunoileal bypass increases the abundance of gut Escherichia coli and Ruminococcus gnavus and the levels of serum glycine, histidine, and glutamine in T2DM rats; and decreases the abundance of Prevotella copri and the levels of serum branched chain amino acids, which are significantly related to the improvement of islet β-cell function in T2DM rats. Our results suggest that amino acid metabolism may contribute to the islet β-cell function in T2DM rats after modified jejunoileal bypass and that improving gut microbiota composition is a potential therapeutic strategy for T2DM.

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