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SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy.
EBioMedicine
January 2025
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang, 110001, China; Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, 110001, China; Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, 110001, China. Electronic address:
Background: Although antiretroviral therapy (ART) effectively inhibits viral replication, it does not fully mitigate the immunosenescence instigated by HIV infection. Cellular metabolism regulates cellular differentiation, survival, and senescence. Serine hydroxymethyltransferase 2 (SHMT2) is the first key enzyme for the entry of serine into the mitochondria from the de novo synthesis pathway that orchestrates its conversion glutathione (GSH), a key molecule in neutralising ROS and ensuring the stability of the immune system.
View Article and Find Full Text PDFBinding of a potential antibacterial drug, mangiferin, to serine hydroxymethyltransferase from Enterococcus faecium.
Biochem Biophys Res Commun
January 2025
Division of Biomedical Measurements and Diagnostics, Graduate School of Biomedical Engineering, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. Electronic address:
Serine hydroxymethyltransferase (SHMT) plays a critical role in the 1C metabolism pathway. This pathway is involved in the synthesis of many amino and nucleic acids, and SHMT is considered a target for drugs through folate metabolism, especially for cancer and malaria. A detailed analysis of the interactions between SHMTs and drugs will greatly contribute to the development of new drugs.
View Article and Find Full Text PDFA recombinant L-threonine aldolase with high catalytic efficiency for the asymmetric synthesis of L-threo-phenylserine and L-threo-4-fluorophenylserine.
Biotechnol Lett
December 2024
Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China.
Objectives: To develop robust variants of L-threonine aldolases (L-TAs), potent catalysts for synthesizing asymmetric β-hydroxy-α-amino acids, it is necessary to identify critical residues beyond the known active site residues.
Results: Through virtual screening, a neglected residue Asn305, was identified as critical for catalytic efficiency. Subsequent site-saturation mutagenesis led to a potent variant N305R which exhibited excellent conversions of 88% (87%) and 80% (94%) for the synthesis of L-threo-phenylserine and L-threo-4-fluorophenylserine respectively.
Mild neurodevelopmental disorder due to reduced SHMT2 enzymatic activity caused by novel compound heterozygous variants: expanding the phenotypic spectrum.
Neurogenetics
November 2024
Key Laboratory for Birth Defects Research and Prevention of the National Health Commission, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, PR China.
Biallelic variants in SHMT2 cause neurodevelopmental disorders with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB; OMIM: 619121). This recently described metabolic disorder are characterized by severe intellectual disability, microcephaly, spastic paraplegia, peripheral neuropathy, corpus callosum dysgenesis, facial and limb deformities, and progressive hypertrophic cardiomyopathy. Herein we describe the clinical characteristics of a 13 years old patient with novel compound heterozygous SHMT2 missense variants (c.
View Article and Find Full Text PDFElucidation of the Role of SHMT2 in L-Serine Homeostasis in Hypoxic Hepa1-6 Cells.
Int J Mol Sci
November 2024
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Hypoxia is a characteristic feature of malignancy; however, its effect on metabolism remains unclear. In this study, Hepa1-6 cells were cultured under hypoxic conditions and their metabolites were analyzed. Elevated levels of L-serine along with increased glycolytic activity are prominent features of hypoxia.
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