Ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates (dNDPs). The Escherichia coli class Ia RNR uses a mechanism of radical propagation by which a cysteine in the active site of the RNR large (α2) subunit is transiently oxidized by a stable tyrosyl radical (Y•) in the RNR small (β2) subunit over a 35-Å pathway of redox-active amino acids: Y122• ↔ [W48?] ↔ Y356 in β2 to Y731 ↔ Y730 ↔ C439 in α2. When 3-aminotyrosine (NH2Y) is incorporated in place of Y730, a long-lived NH2Y730• is generated in α2 in the presence of wild-type (wt)-β2, substrate, and effector. This radical intermediate is chemically and kinetically competent to generate dNDPs. Herein, evidence is presented that NH2Y730• induces formation of a kinetically stable α2β2 complex. Under conditions that generate NH2Y730•, binding between Y730NH2Y-α2 and wt-β2 is 25-fold tighter (Kd = 7 nM) than for wt-α2
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593893 | PMC |
| http://dx.doi.org/10.1073/pnas.1220691110 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Computer Simulation of Sulfated Cyclodextrin-Based Enantioselective Separation of Weak Bases With Partial, High-Concentration Filling of the Chiral Selector and Analyte Detection on the Cathodic Side.
Electrophoresis
January 2025
Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Computer simulation was utilized to characterize the electrophoretic processes occurring during the enantioselective capillary electrophoresis-mass spectrometry (CE-MS) analysis of ketamine, norketamine, and hydroxynorketamine in a system with partial filling of the capillary with 19 mM (equals 5%) of highly sulfated γ-cyclodextrin (HS-γ-CD) and analyte detection on the cathodic side. Provided that the sample is applied without or with a small amount of the chiral selector, analytes become quickly focused and separated in the thereby formed HS-γ-CD gradient at the cathodic end of the sample compartment. This gradient broadens with time, remains stationary, and gradually reduces its span from the lower side due to diffusion such that analytes with high affinity to the anionic selector become released onto the other side of the focusing gradient where anionic migration and defocusing occur concomitantly.
View Article and Find Full Text PDFDD-PRiSM: a deep learning framework for decomposition and prediction of synergistic drug combinations.
Brief Bioinform
November 2024
School of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology (GIST), Buk-gu, Gwangju 61005, Republic of Korea.
Combination therapies have emerged as a promising approach for treating complex diseases, particularly cancer. However, predicting the efficacy and safety profiles of these therapies remains a significant challenge, primarily because of the complex interactions among drugs and their wide-ranging effects. To address this issue, we introduce DD-PRiSM (Decomposition of Drug-Pair Response into Synergy and Monotherapy effect), a deep-learning pipeline that predicts the effects of combination therapy.
View Article and Find Full Text PDFIntegrating scRNA-seq and scATAC-seq with inter-type attention heterogeneous graph neural networks.
Brief Bioinform
November 2024
Department of Electronic Engineering, Tsinghua University, 100084 Beijing, China.
Single-cell multi-omics techniques, which enable the simultaneous measurement of multiple modalities such as RNA gene expression and Assay for Transposase-Accessible Chromatin (ATAC) within individual cells, have become a powerful tool for deciphering the intricate complexity of cellular systems. Most current methods rely on motif databases to establish cross-modality relationships between genes from RNA-seq data and peaks from ATAC-seq data. However, these approaches are constrained by incomplete database coverage, particularly for novel or poorly characterized relationships.
View Article and Find Full Text PDFSpatio-Temporal Change of Skin and Oral Microbiota: A Longitudinal Study of Microbial Diversity and Stability.
Electrophoresis
January 2025
Institute of Forensic Science, Fudan University, Shanghai, P. R. China.
The human skin and oral cavity harbor complex microbial communities, which exist in dynamic equilibrium with the host's physiological state and the external environment. This study investigates the microbial atlas of human skin and oral cavities using samples collected over a 10-month period, aiming to assess how both internal and external factors influence the human microbiome. We examined bacterial community diversity and stability across various body sites, including palm and nasal skin, saliva, and oral epithelial cells, during environmental changes and a COVID-19 pandemic.
View Article and Find Full Text PDFMolecular Identification and Antifungal Susceptibility of Fusarium spp. Clinical Isolates.
Mycoses
January 2025
Clinical Microbiology Laboratory, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Background: Accurate identification of Fusarium species requires molecular identification. Treating fusariosis is challenging due to widespread antifungal resistance, high rates of treatment failure, and insufficient information relating antifungal susceptibility to the clinical outcome. Despite recent outbreaks in Mexico, there is limited information on epidemiology and antifungal susceptibility testing (AST).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!