The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform
Leszek Rychlewski - One of the best experts on this subject based on the ideXlab platform.
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unusual evolutionary history of the trna splicing endonuclease enda relationship to the laglidadg and pd d e xk Deoxyribonucleases
Protein Science, 2001Co-Authors: Janusz M Bujnicki, Leszek RychlewskiAbstract:The tRNA splicing endoribonuclease EndA from Methanococcus jannaschii is a homotetramer formed via heterologous interaction between the two pairs of homodimers. Each monomer consists of two alpha/beta domains, the N-terminal domain (NTD) and the C-terminal domain (CTD) containing the RNase A-like active site. Comparison of the EndA coordinates with the publicly available protein structure database revealed the similarity of both domains to site-specific Deoxyribonucleases: the NTD to the LAGLIDADG family and the CTD to the PD-(D/E)XK family. Superposition of the NTD on the catalytic domain of LAGLIDADG homing endonucleases allowed a suggestion to be made about which amino acid residues of the tRNA splicing nuclease might participate in formation of a presumptive cryptic deoxyribonuclease active site. On the other hand, the CTD and PD-(D/E)XK endonucleases, represented by restriction enzymes and a phage lambda exonuclease, were shown to share extensive similarities of the structural framework, to which entirely different active sites might be attached in two alternative locations. These findings suggest that EndA evolved from a fusion protein with at least two distinct endonuclease activities: the ribonuclease, which made it an essential "antitoxin" for the cells whose RNA genes were interrupted by introns, and the deoxyribonuclease, which provided the means for homing-like mobility. The residues of the noncatalytic CTDs from the positions corresponding to the catalytic side chains in PD-(D/E)XK Deoxyribonucleases map to the surface at the opposite side to the tRNA binding site, for which no function has been implicated. Many restriction enzymes from the PD-(D/E)XK superfamily might have the potential to maintain an additional active or binding site at the face opposite the deoxyribonuclease active site, a property that can be utilized in protein engineering.
Timur I. Abdullin - One of the best experts on this subject based on the ideXlab platform.
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Electrochemical sensor for blood Deoxyribonucleases: design and application to the diagnosis of autoimmune thyroiditis
Analytical and bioanalytical chemistry, 2011Co-Authors: Irina I. Shakhmaeva, Diana V. Saifullina, Liliya I. Sattarova, Timur I. AbdullinAbstract:We designed an electrochemical sensor based on a carbon nanotube modified electrode (ME) to analyze DNA-cleaving activity. The cleavage of high molecular weight DNA resulted in an increase in the oxidation current from DNA guanine nucleotides due to a change in DNA adsorptive behavior on the surface of the ME. DNA digestion with DNAse I was accompanied by a linear increase in the DNA signal in proportion to the enzyme activity. We then proposed an assay based on the sensor for the direct assessment of the total deoxyribonuclease activity of blood serum as well as the separate detection of DNAse I and DNA abzymes. The assay was applied to analyze Deoxyribonucleases in sera from 21 healthy donors and 17 patients with autoimmune thyroiditis. Our results show that the response of the sensor to DNA cleavage by blood Deoxyribonucleases is a promising diagnostic criterion for autoimmune thyroiditis. This sensor can be implemented in a disposable screen-printed electrode format for application in clinical laboratories.
Janusz M Bujnicki - One of the best experts on this subject based on the ideXlab platform.
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unusual evolutionary history of the trna splicing endonuclease enda relationship to the laglidadg and pd d e xk Deoxyribonucleases
Protein Science, 2001Co-Authors: Janusz M Bujnicki, Leszek RychlewskiAbstract:The tRNA splicing endoribonuclease EndA from Methanococcus jannaschii is a homotetramer formed via heterologous interaction between the two pairs of homodimers. Each monomer consists of two alpha/beta domains, the N-terminal domain (NTD) and the C-terminal domain (CTD) containing the RNase A-like active site. Comparison of the EndA coordinates with the publicly available protein structure database revealed the similarity of both domains to site-specific Deoxyribonucleases: the NTD to the LAGLIDADG family and the CTD to the PD-(D/E)XK family. Superposition of the NTD on the catalytic domain of LAGLIDADG homing endonucleases allowed a suggestion to be made about which amino acid residues of the tRNA splicing nuclease might participate in formation of a presumptive cryptic deoxyribonuclease active site. On the other hand, the CTD and PD-(D/E)XK endonucleases, represented by restriction enzymes and a phage lambda exonuclease, were shown to share extensive similarities of the structural framework, to which entirely different active sites might be attached in two alternative locations. These findings suggest that EndA evolved from a fusion protein with at least two distinct endonuclease activities: the ribonuclease, which made it an essential "antitoxin" for the cells whose RNA genes were interrupted by introns, and the deoxyribonuclease, which provided the means for homing-like mobility. The residues of the noncatalytic CTDs from the positions corresponding to the catalytic side chains in PD-(D/E)XK Deoxyribonucleases map to the surface at the opposite side to the tRNA binding site, for which no function has been implicated. Many restriction enzymes from the PD-(D/E)XK superfamily might have the potential to maintain an additional active or binding site at the face opposite the deoxyribonuclease active site, a property that can be utilized in protein engineering.
Shigekazu Nagata - One of the best experts on this subject based on the ideXlab platform.
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dna degradation and its defects
Cold Spring Harbor Perspectives in Biology, 2014Co-Authors: Kohki Kawane, Kou Motani, Shigekazu NagataAbstract:DNA is one of the most essential molecules in organisms, containing all the information necessary for organisms to live. It replicates and provides a mechanism for heredity and evolution. Various events cause the degradation of DNA into nucleotides. DNA also has a darker side that has only recently been recognized; DNA that is not properly degraded causes various diseases. In this review, we discuss four Deoxyribonucleases that function in the nucleus, cytosol, and lysosomes, and how undigested DNA causes such diseases as cancer, cataract, and autoinflammation. Studies on the biochemical and physiological functions of Deoxyribonucleases should continue to increase our understanding of cellular functions and human diseases.
Ryo Kinoshitadaitoku - One of the best experts on this subject based on the ideXlab platform.
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group a streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps
Scientific Reports, 2020Co-Authors: Mototsugu Tanaka, Ryo Kinoshitadaitoku, Kotaro Kiga, Takahito Sanada, Bo Zhu, Tokuju OkanoAbstract:Group A Streptococcus (GAS) secretes Deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.