Category: 452-06-2

Lund, Paul E.; Chatterjee, Surajit; Daher, May; Walter, Nils G. published the artcile< Protein unties the pseudoknot: S1-mediated unfolding of RNA higher order structure>, Electric Literature of 452-06-2, the main research area is proteinS1 pseudoknot unfolding RNA preQ1 riboswitch conformation modeling Escherichia.

Ribosomal protein S1 plays important roles in the translation initiation step of many Escherichia coli mRNAs, particularly those with weak Shine-Dalgarno sequences or structured 5′ UTRs, in addition to a variety of cellular processes beyond the ribosome. In all cases, the RNA-binding activity of S1 is a central feature of its function. While sequence determinants of S1 affinity and many elements of the interactions of S1 with simple secondary structures are known, mechanistic details of the protein’s interactions with RNAs of more complex secondary and tertiary structure are less understood. Here, we investigate the interaction of S1 with the well-characterized H-type pseudoknot of a class-I translational preQ1 riboswitch as a highly structured RNA model whose conformation and structural dynamics can be tuned by the addition of ligands of varying binding affinity, particularly preQ1, guanine, and 2,6-diaminopurine. Combining biochem. and single mol. fluorescence approaches, we show that S1 preferentially interacts with the less folded form of the pseudoknot and promotes a dynamic, partially unfolded conformation. The ability of S1 to unfold the RNA is inversely correlated with the structural stability of the pseudoknot. These mechanistic insights delineate the scope and limitations of S1-chaperoned unfolding of structured RNAs.

Nucleic Acids Research published new progress about 5′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Electric Literature of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Lo, Chen-Yu; Gao, Yang published the artcile< DNA Polymerase-Parental DNA Interaction Is Essential for Helicase-Polymerase Coupling during Bacteriophage T7 DNA Replication>, Reference of 452-06-2, the main research area is bacteriophage T7 DNA replication polymerase helicase coupling; DNA replication; bacteriophage T7; helicase; polymerase.

DNA helicase and polymerase work cooperatively at the replication fork to perform leading-strand DNA synthesis. It was believed that the helicase migrates to the forefront of the replication fork where it unwinds the duplex to provide templates for DNA polymerases. However, the mol. basis of the helicase-polymerase coupling is not fully understood. The recently elucidated T7 replisome structure suggests that the helicase and polymerase sandwich parental DNA and each enzyme pulls a daughter strand in opposite directions. Interestingly, the T7 polymerase, but not the helicase, carries the parental DNA with a pos. charged cleft and stacks at the fork opening using a β-hairpin loop. Here, we created and characterized T7 polymerases each with a perturbed β-hairpin loop and pos. charged cleft. Mutations on both structural elements significantly reduced the strand-displacement synthesis by T7 polymerase but had only a minor effect on DNA synthesis performed against a linear DNA substrate. Moreover, the aforementioned mutations eliminated synergistic helicase-polymerase binding and unwinding at the DNA fork and processive fork progressions. Thus, our data suggested that T7 polymerase plays a dominant role in helicase-polymerase coupling and replisome progression.

International Journal of Molecular Sciences published new progress about Coliphage T7. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Reference of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Pagano, Bruno; Iaccarino, Nunzia; Di Porzio, Anna; Randazzo, Antonio; Amato, Jussara published the artcile< Screening of DNA G-quadruplex stabilizing ligands by nano differential scanning fluorimetry>, Application In Synthesis of 452-06-2, the main research area is DNA G quadruplex stabilizing ligand nano differential scanning fluorimetry.

G-quadruplex (G4) nucleic acid structures are involved in a number of different diseases and their drug-induced stabilization is deemed to be a promising therapeutic approach. Herein is reported a proof of principle study on the use of nano differential scanning fluorimetry for a rapid and accurate anal. of G4-stabilizing ligands, exploiting the fluorescence properties of a 2-aminopurine modified G4-forming oligonucleotide.

Analyst (Cambridge, United Kingdom) published new progress about DNA Role: ANT (Analyte), BSU (Biological Study, Unclassified), ANST (Analytical Study), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Application In Synthesis of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhu, Mei; Dong, Biao; Zhang, Guo-Ning; Wang, Ju-Xian; Cen, Shan; Wang, Yu-Cheng published the artcile< Synthesis and biological evaluation of new HIV-1 protease inhibitors with purine bases as P2-ligands>, Reference of 452-06-2, the main research area is HIV1 protease inhibitor purine base derivative; Biological evaluation; HIV-1 protease inhibitors; Purine bases.

Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j (I – III, resp.) containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2′-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC50 43 nM, 42 nM and 68 nM in vitro, resp.

Bioorganic & Medicinal Chemistry Letters published new progress about AIDS (disease). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Reference of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Li-juan; Ren, Ming; Wang, Hou-xiu; Qiu, Jian-Ge; Jiang, BingHua; Zhang, Chun-yang published the artcile< Construction of a quencher-free cascade amplification system for highly specific and sensitive detection of serum circulating miRNAs>, Computed Properties of 452-06-2, the main research area is microRNA sequence strand displacement amplification blood human neoplasm diagnosis.

Circulating miRNAs are a newly emerging class of noninvasive biomarkers, and the accurate quantification of their expression is essential to the biol. research and early clinic diagnosis. Herein, we demonstrate the construction of a quencher-free cascade amplification system for highly sensitive detection of serum circulating miRNAs. The target miRNA can hybridize with the linear probe to induce the cyclic strand displacement amplification (SDA) (cycle I) for the production of the binding probes. The binding probe can subsequently react with the 2-aminopurine (2-AP)-hairpin probe to induce the recycling exonuclease cleavage of 2-AP-hairpin probes (cycle II), releasing the triggers and 2-AP mols. simultaneously. The released trigger can hybridize with the free linear probe to start new cycles I and II amplifications. Through multiple rounds of cascade amplifications, a large number of 2-AP mols. are released, generating an enhanced fluorescence signal. This method exhibits a large dynamic range of 8 orders of magnitude and a detection limit of 0.16 aM. It can differentiate a single-base mismatch in miR-486-5p, quantify miR-486-5p in lung cancer cells at various stages, and even discriminate the expressions of serum circulating miR-486-5p in healthy persons from that in nonsmall-cell lung carcinoma (NSCLC) patients. Moreover, this assay can be rapidly carried out in one step under isothermal condition in a label-free manner, holding promising applications in point-of-care diagnosis and prognosis of lung cancers.

Analytical Chemistry (Washington, DC, United States) published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (ARHGAP5). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Computed Properties of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Czernecki, Dariusz; Bonhomme, Frederic; Kaminski, Pierre-Alexandre; Delarue, Marc published the artcile< Characterization of a triad of genes in cyanophage S-2L sufficient to replace adenine by 2-aminoadenine in bacterial DNA>, Recommanded Product: 7H-Purin-2-amine, the main research area is .

Abstract: Cyanophage S-2L is known to profoundly alter the biophys. properties of its DNA by replacing all adenines (A) with 2-aminoadenines (Z), which still pair with thymines but with a triple hydrogen bond. It was recently demonstrated that a homolog of adenylosuccinate synthetase (PurZ) and a dATP triphosphohydrolase (DatZ) are two important pieces of the metabolism of 2-aminoadenine, participating in the synthesis of ZTGC-DNA. Here, we determine that S-2L PurZ can use either dATP or ATP as a source of energy, thereby also depleting the pool of nucleotides in dATP. Furthermore, we identify a conserved gene (mazZ) located between purZ and datZ genes in S-2L and related phage genomes. We show that it encodes a (d)GTP-specific diphosphohydrolase, thereby providing the substrate of PurZ in the 2-aminoadenine synthesis pathway. High-resolution crystal structures of S-2L PurZ and MazZ with their resp. substrates provide a rationale for their specificities. The Z-cluster made of these three genes – datZ, mazZ and purZ – was expressed in E. coli, resulting in a successful incorporation of 2-aminoadenine in the bacterial chromosomal and plasmidic DNA. This work opens the possibility to study synthetic organisms containing ZTGC-DNA.

Nature Communications published new progress about 452-06-2. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Jianzhong; Wang, Xingyu; Pang, Laixue; Zhang, John Z. H.; Zhu, Tong published the artcile< Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations>, Related Products of 452-06-2, the main research area is guanine riboswitch mutation ligand binding mol dynamics simulation.

Riboswitches can regulate gene expression by direct and specific interactions with ligands and have recently attracted interest as potential drug targets for antibacterial. In this work, mol. dynamics (MD) simulations, free energy perturbation (FEP) and mol. mechanics generalized Born surface area (MM-GBSA) methods were integrated to probe the effect of mutations on the binding of ligands to guanine riboswitch (GR). The results not only show that binding free energies predicted by FEP and MMGBSA obtain an excellent correlation, but also indicate that mutations involved in the current study can strengthen the binding affinity of ligands GR. Residue-based free energy decomposition was applied to compute ligand-nucleotide interactions and the results suggest that mutations highly affect interactions of ligands with key nucleotides U22, U51 and C74. Dynamics analyses based on MD trajectories indicate that mutations not only regulate the structural flexibility but also change the internal motion modes of GR, especially for the structures J12, J23 and J31, which implies that the aptamer domain activity of GR is extremely plastic and thus readily tunable by nucleotide mutations. This study is expected to provide useful mol. basis and dynamics information for the understanding of the function of GR and possibility as potential drug targets for antibacterial.

Nucleic Acids Research published new progress about Free energy of binding. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Related Products of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tan, Ying; You, Changjun; Park, Jiyeong; Kim, Hyun Suk; Guo, Su; Scharer, Orlando D.; Wang, Yinsheng published the artcile< Transcriptional Perturbations of 2,6-Diaminopurine and 2-Aminopurine>, Recommanded Product: 7H-Purin-2-amine, the main research area is transcription diaminopurine aminopurine.

2,6-Diaminopurine (Z) is a naturally occurring adenine (A) analog that bacteriophages employ in place of A in their genetic alphabet. Recent discoveries of biogenesis pathways of Z in bacteriophages have stimulated substantial research interest in this DNA modification. Here, the authors systematically examined the effects of Z on the efficiency and fidelity of DNA transcription. The authors’ results showed that Z exhibited no mutagenic yet substantial inhibitory effects on transcription mediated by purified T7 RNA polymerase and by human RNA polymerase II in HeLa nuclear extracts and in human cells. A structurally related adenine analog, 2-aminopurine (2AP), strongly blocked T7 RNA polymerase but did not impede human RNA polymerase ii in vitro or in human cells, where no mutant transcript could be detected. The lack of mutagenic consequence and the presence of a strong blockage effect of Z on transcription suggest a role of Z in transcriptional regulation. Z is also subjected to removal by transcription-coupled nucleotide-excision repair (TC-NER), but not global-genome NER in human cells. The authors’ findings provide new insight into the effects of Z on transcription and its potential biol. functions.

ACS Chemical Biology published new progress about Homo sapiens. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Subramani, Vinod Kumar; Ravichandran, Subramaniyam; Bansal, Varun; Kim, Kyeong Kyu published the artcile< Chemical-induced formation of BZ-junction with base extrusion>, Recommanded Product: 7H-Purin-2-amine, the main research area is spermine ethanol methanol cobalt sodium perchlorate; 2-Aminopurine; BZ-Junction; Base-extrusion; Z-DNA; Z-DNA junction; Z-inducer.

The crystal structure of BZ-junction reveals that left-handed Z-DNA stabilized by Z-DNA binding domain (Zα) is continuously stacked to right-handed B-DNA with AT bases’ extrusion in the junction site. However, this structure might not fully represent the BZ-junction in solution due to the possibility of the junction formation either by crystal packing or Zα interaction. Therefore, we investigated BZ-junction in solution with chem. Z-DNA inducers using CD and 2-aminopurine base-extrusion assay. We confirmed the formation of Z-DNA and BZ-junction with base-extrusion by chem. Z-DNA inducers. However, neither typical Z-DNA nor base-extrusion could be detected with some inducers such as spermine, suggesting that the energy barrier for the formation of the BZ junction might vary depending on the Z-DNA induction conditions.

Biochemical and Biophysical Research Communications published new progress about Crystal structure. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ouzon-Shubeita, Hala; Schmaltz, Lillian F.; Lee, Seongmin published the artcile< Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4>, SDS of cas: 452-06-2, the main research area is methyl CpG binding domain 4 DNA base excision repair; DNA glycosylase; base excision repair; substrate recognition.

G:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guanine is stabilized by Arg468 of MBD4. To gain further insights into the mismatch discrimination mechanism of MBD4, we assessed the glycosylase activity of MBD4 toward various base pairs. In addition, we determined a crystal structure of MBD4 bound to T:O6-methylguanine-containing DNA, which suggests the O6 and N2 of purine and the O4 of pyrimidine are required to be a substrate for MBD4. To understand the role of the Arg468 finger in catalysis, we evaluated the glycosylase activity of MBD4 mutants, which revealed the guanidinium moiety of Arg468 may play an important role in catalysis. D560N/R468K MBD4 bound to T:G mismatched DNA shows that the side chain amine moiety of the Lys stabilizes the flipped-out thymine by a water-mediated phosphate pinching, while the backbone carbonyl oxygen of the Lys engages in hydrogen bonds with N2 of the estranged guanine. Comparison of various DNA glycosylase structures implies the guanidinium and amine moieties of Arg and Lys, resp., may involve in discriminating between substrate mismatches and nonsubstrate base pairs.

Biochemical Journal published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (MBD4). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, SDS of cas: 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem