Category: 58-97-9

Li, Lei; Huang, Kai-Lieh; Gao, Yipeng; Cui, Ya; Wang, Gao; Elrod, Nathan D.; Li, Yumei; Chen, Yiling Elaine; Ji, Ping; Peng, Fanglue; Russell, William K.; Wagner, Eric J.; Li, Wei published the artcile< An atlas of alternative polyadenylation quantitative trait loci contributing to complex trait and disease heritability>, SDS of cas: 58-97-9, the main research area is human alternative polyadenylation QTL linkage mapping disease heritability.

Genome-wide association studies have identified thousands of noncoding variants associated with human traits and diseases. However, the functional interpretation of these variants is a major challenge. Here, we constructed a multi-tissue atlas of human 3’UTR alternative polyadenylation (APA) quant. trait loci (3’aQTLs), containing approx. 0.4 million common genetic variants associated with the APA of target genes, identified in 46 tissues isolated from 467 individuals (Genotype-Tissue Expression Project). Mechanistically, 3’aQTLs can alter poly(A) motifs, RNA secondary structure and RNA-binding protein-binding sites, leading to thousands of APA changes. Our CRISPR-based experiments indicate that such 3’aQTLs can alter APA regulation. Furthermore, we demonstrate that mapping 3’aQTLs can identify APA regulators, such as La-related protein 4. Finally, 3’aQTLs are colocalized with approx. 16.1% of trait-associated variants and are largely distinct from other QTLs, such as expression QTLs. Together, our findings show that 3’aQTLs contribute substantially to the mol. mechanisms underlying human complex traits and diseases.

Nature Geneticspublished new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, SDS of cas: 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Ahn, Woo-Chan; Aroli, Shashanka; Kim, Jin-Hahn; Moon, Jeong Hee; Lee, Ga Seal; Lee, Min-Ho; Sang, Pau Biak; Oh, Byung-Ha; Varshney, Umesh; Woo, Eui-Jeon published the artcile< Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision>, Application of C9H13N2O9P, the main research area is covalent binding uracil DNA glycosylase udgx abasic upon excision.

Uracil DNA glycosylases (UDGs) are important DNA repair enzymes that excise uracil from DNA, yielding an abasic site. Recently, UdgX, an unconventional UDG with extremely tight binding to DNA containing uracil, was discovered. The structure of UdgX from Mycobacterium smegmatis in complex with DNA shows an overall similarity to that of family 4 UDGs except for a protruding loop at the entrance of the uracil-binding pocket. Surprisingly, H109 in the loop was found to make a covalent bond to the abasic site to form a stable intermediate, while the excised uracil remained in the pocket of the active site. H109 functions as a nucleophile to attack the oxocarbenium ion, substituting for the catalytic water mol. found in other UDGs. To our knowledge, this change from a catalytic water attack to a direct nucleophilic attack by the histidine residue is unprecedented. UdgX utilizes a unique mechanism of protecting cytotoxic abasic sites from exposure to the cellular environment.

Nature Chemical Biologypublished new progress about Enzyme functional sites, active. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Application of C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Bonin, Jeffrey P.; Sapienza, Paul J.; Wilkerson, Emily; Goldfarb, Dennis; Wang, Li; Herring, Laura; Chen, Xian; Major, Michael B.; Lee, Andrew L. published the artcile< Positive Cooperativity in Substrate Binding by Human Thymidylate Synthase>, Reference of 58-97-9, the main research area is pos cooperativity substrate binding thymidylate synthase.

Thymidylate synthase (TS) catalyzes the production of the nucleotide dTMP from deoxyuridine monophosphate (dUMP), making the enzyme necessary for DNA replication and consequently a target for cancer therapeutics. TSs are homodimers with active sites separated by ∼30 Å. Reports of half-the-sites activity in TSs from multiple species demonstrate the presence of allosteric communication between the active sites of this enzyme. A simple explanation for the neg. allosteric regulation occurring in half-the-sites activity would be that the two substrates bind with neg. cooperativity. However, previous work on Escherichia coli TS revealed that dUMP substrate binds without cooperativity. To gain further insight into TS allosteric function, binding cooperativity in human TS is examined here. Isothermal titration calorimetry and two-dimensional lineshape anal. of NMR titration spectra are used to characterize the thermodn. of dUMP binding, with a focus on quantification of cooperativity between the two substrate binding events. We find that human TS binds dUMP with ∼9-fold entropically driven pos. cooperativity (ρITC = 9 ± 1, ρNMR = 7 ± 1), in contrast to the apparent strong neg. cooperativity reported previously. Our work further demonstrates the necessity of globally fitting isotherms collected under various conditions, as well as accurate determination of binding competent protein concentration, for calorimetric characterization of homotropic cooperative binding. Notably, an initial curvature of the isotherm is found to be indicative of pos. cooperative binding. Two-dimensional lineshape anal. NMR is also found to be an informative tool for quantifying binding cooperativity, particularly in cases in which bound intermediates yield unique resonances.

Biophysical Journalpublished new progress about Enzyme functional sites, active. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Reference of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem