Synthesis of a Cyclic Dinucleotide Analogue with Ambiguous Bases, 5-Aminoimidazole-4-carboxamide

2021 ◽  
Author(s):  
Noriko S. Tarashima ◽  
Yusuke Kumanomido ◽  
Katsuyuki Nakashima ◽  
Yoshiyuki Tanaka ◽  
Noriaki Minakawa
Keyword(s):  
Cyclic Dinucleotide

Unraveling cGAS catalytic mechanism upon DNA activation through molecular dynamics simulations

2021 ◽  
Author(s):  
Jordi Soler ◽  
Pedro Paiva ◽  
Maria Joao Joao Ramos ◽  
Pedro Alexandrino Fernandes ◽  
Marie Brut
Keyword(s):  
Molecular Dynamics ◽  
Dna Binding ◽  
Molecular Dynamics Simulations ◽  
Cyclic Gmp ◽  
Catalytic Mechanism ◽  
System P ◽  
Dynamics Simulations ◽  
Cyclic Dinucleotide

Cyclic GMP-AMP Synthase (cGAS) is activated upon DNA binding and catalyzes the synthesis of 2’,3’-cGAMP from GTP and ATP. This cyclic dinucleotide is a messenger that triggers the autoimmune system...

scholarly journals Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hiroki Omura ◽  
Daisuke Oikawa ◽  
Takanori Nakane ◽  
Megumi Kato ◽  
Ryohei Ishii ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Immune Receptor ◽  
Cyclic Dinucleotide

Cyclic Dinucleotide Signaling in Mycobacteria

2020 ◽  
pp. 3-25
Author(s):  
Anushya Petchiappan ◽  
Avisek Mahapa ◽  
Dipankar Chatterji
Keyword(s):  
Cyclic Dinucleotide

Synthesis of cyclic dimeric methyl morpholinoside—a common synthetic precursor to cyclic dinucleotide analogs

2014 ◽  
Vol 55 (35) ◽  
pp. 4966-4968 ◽  
Author(s):  
Charles R. Kinzie ◽  
Andrew D. Steele ◽  
Stacy M. Pasciolla ◽  
William M. Wuest
Keyword(s):  
Cyclic Dinucleotide

Conformational Analysis of the 3′-5′-Cyclic Dinucleotide d by Means of Molecular Mechanics

1990 ◽  
Vol 8 (2) ◽  
pp. 233-251 ◽  
Author(s):  
M. J.J. Blommers ◽  
H. J. Bruins Slot ◽  
G. A. van der Marel ◽  
J. H. van Boom ◽  
C. W. Hilbers
Keyword(s):  
Conformational Analysis ◽  
Molecular Mechanics ◽  
Cyclic Dinucleotide

scholarly journals Sugar-mediated regulation of a c-di-GMP phosphodiesterase in Vibrio cholerae

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyoo Heo ◽  
Young-Ha Park ◽  
Kyung-Ah Lee ◽  
Joonwon Kim ◽  
Hyeong-In Ham ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Carbon Sources ◽  
Phosphotransferase System ◽  
Host Colonization ◽  
Host Immune Responses ◽  
Gut Colonization ◽  
Host Diet ◽  
Underlying Mechanisms ◽  
Cyclic Dinucleotide

AbstractBiofilm formation protects bacteria from stresses including antibiotics and host immune responses. Carbon sources can modulate biofilm formation and host colonization in Vibrio cholerae, but the underlying mechanisms remain unclear. Here, we show that EIIAGlc, a component of the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS), regulates the intracellular concentration of the cyclic dinucleotide c-di-GMP, and thus biofilm formation. The availability of preferred sugars such as glucose affects EIIAGlc phosphorylation state, which in turn modulates the interaction of EIIAGlc with a c-di-GMP phosphodiesterase (hereafter referred to as PdeS). In a Drosophila model of V. cholerae infection, sugars in the host diet regulate gut colonization in a manner dependent on the PdeS-EIIAGlc interaction. Our results shed light into the mechanisms by which some nutrients regulate biofilm formation and host colonization.

scholarly journals Cyclic Dinucleotide–Adjuvanted Dengue Virus Nonstructural Protein 1 Induces Protective Antibody and T Cell Responses

2019 ◽  
Vol 202 (4) ◽  
pp. 1153-1162 ◽  
Author(s):  
Diego A. Espinosa ◽  
P. Robert Beatty ◽  
Gabrielle L. Reiner ◽  
Kelsey E. Sivick ◽  
Laura Hix Glickman ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Nonstructural Protein ◽  
T Cell Responses ◽  
Protective Antibody ◽  
Cell Responses ◽  
Nonstructural Protein 1 ◽  
Cyclic Dinucleotide

scholarly journals DNA-induced 2′3′-cGAMP enhances haplotype-specific human STING cleavage by dengue protease

2020 ◽  
Vol 117 (27) ◽  
pp. 15947-15954 ◽  
Author(s):  
Chan-I Su ◽  
Yu-Ting Kao ◽  
Chao-Chen Chang ◽  
Yao Chang ◽  
Tzong-Shiann Ho ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Rna Virus ◽  
Adaptor Protein ◽  
Denv Infection ◽  
Host Immunity ◽  
Virus Reactivation ◽  
Dna Virus ◽  
Exogenous Dna ◽  
Taiwanese People ◽  
Cyclic Dinucleotide

The cytosolic DNA sensor cGMP-AMP synthase (cGAS) synthesizes the noncanonical cyclic dinucleotide 2′3′-cGAMP to activate the adaptor protein stimulator of IFN genes (STING), thus awakening host immunity in response to DNA pathogen infection. However, dengue virus (DENV), an RNA virus without a DNA stage in its life cycle, also manipulates cGAS-STING–mediated innate immunity by proteolytic degradation of STING. Here, we found that the sensitivity of STING to DENV protease varied with different human STING haplotypes. Exogenous DNA further enhanced DENV protease’s ability to interact and cleave protease-sensitive STING. DNA-enhanced STING cleavage was reduced in cGAS-knockdown cells and triggered by the cGAS product 2′3′-cGAMP. The source of DNA may not be endogenous mitochondrial DNA but rather exogenous reactivated viral DNA. Cells producing 2′3′-cGAMP by overexpressing cGAS or with DNA virus reactivation enhanced STING cleavage in neighboring cells harboring DENV protease. DENV infection reduced host innate immunity in cells with the protease-sensitive STING haplotype, whose homozygote genotype frequency was found significantly reduced in Taiwanese people with dengue fever. Therefore, the human STING genetic background and DNA pathogen coinfection may be the missing links contributing to DENV pathogenesis.

scholarly journals Cyclic Dinucleotide-Controlled Regulatory Pathways in Streptomyces Species

2015 ◽  
Vol 198 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Natalia Tschowri
Keyword(s):  
Cell Wall ◽  
Current Knowledge ◽  
Second Messengers ◽  
Streptomyces Species ◽  
Content Type ◽  
Regulatory Pathways ◽  
Cellular Processes ◽  
Signal Transduction Networks ◽  
Cyclic Dinucleotides ◽  
Cyclic Dinucleotide

The cyclic dinucleotides cyclic 3′,5′-diguanylate (c-di-GMP) and cyclic 3′,5′-diadenylate (c-di-AMP) have emerged as key components of bacterial signal transduction networks. These closely related second messengers follow the classical general principles of nucleotide signaling by integrating diverse signals into regulatory pathways that control cellular responses to changing environments. They impact distinct cellular processes, with c-di-GMP having an established role in promoting bacterial adhesion and inhibiting motility and c-di-AMP being involved in cell wall metabolism, potassium homeostasis, and DNA repair. The involvement of c-dinucleotides in the physiology of the filamentous, nonmotile streptomycetes remained obscure until recent discoveries showed that c-di-GMP controls the activity of the developmental master regulator BldD and that c-di-AMP determines the level of the resuscitation-promoting factor A(RpfA) cell wall-remodelling enzyme. Here, I summarize our current knowledge of c-dinucleotide signaling inStreptomycesspecies and highlight the important roles of c-di-GMP and c-di-AMP in the biology of these antibiotic-producing, multicellular bacteria.

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