The inhibition of D-glyceraldehyde-3-phosphate dehydrogenase by ATP is of purely mixed type with respect to NAD (Ki=4.9 mM), purely uncompetitive with respect to D-glyceraldehyde-3-phosphate (Ki=9.4 mM) and partially uncompetitive with respect to inorganic phosphate (Ki=6.0 mM). Quinaldate is a purely mixed type inhibitor with respect to both NAD (Ki==10.0 mM) and D-glyceraldehyde-3-phosphate (Ki=15.3 mM), whereas purely non-competitive with respect to inorganic phosphate (Ki=11.0 mM). In the presence of quinaldate a lag period is observed in the time course of enzyme reaction. The duration of this lag period depends on both quinaldate and substrate concentrations.
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ACS Infect Dis
April 2024
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
New antimicrobial strategies are needed to address pathogen resistance to currently used antibiotics. Bacterial central metabolism is a promising target space for the development of agents that selectively target bacterial pathogens. 1-Deoxy-d-xylulose 5-phosphate synthase (DXPS) converts pyruvate and d-glyceraldehyde 3-phosphate (d-GAP) to DXP, which is required for synthesis of essential vitamins and isoprenoids in bacterial pathogens.
View Article and Find Full Text PDFActa Pharmacol Sin
February 2022
Drug Discovery and Design Center, the Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases.
View Article and Find Full Text PDFBiochemistry
March 2021
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
The thiamin diphosphate-dependent enzyme 1-deoxy-d-xylulose 5-phosphate synthase (DXPS) catalyzes the formation of DXP from pyruvate (donor) and d-glyceraldehyde 3-phosphate (d-GAP, acceptor). DXPS is essential in bacteria but absent in human metabolism, highlighting it as a potential antibacterial drug target. The enzyme possesses unique structural and mechanistic features that enable development of selective inhibition strategies and raise interesting questions about DXPS function in bacterial pathogens.
View Article and Find Full Text PDFFront Microbiol
February 2019
Center for Biological Research, Spanish National Research Council, Madrid, Spain.
The ubiquitous and highly abundant glycolytic enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pivotal for the energy and carbon metabolism of most organisms, including human pathogenic bacteria. For bacteria that depend mostly on glycolysis for survival, GAPDH is an attractive target for inhibitor discovery. The availability of high-resolution structures of GAPDH from various pathogenic bacteria is central to the discovery of new antibacterial compounds.
View Article and Find Full Text PDFAcc Chem Res
October 2018
Department of Pharmacology and Molecular Sciences , The Johns Hopkins University School of Medicine, Baltimore , Maryland 21205 , United States.
Antibiotics are the cornerstone of modern healthcare. The 20th century discovery of sulfonamides and β-lactam antibiotics altered human society immensely. Simple bacterial infections were no longer a leading cause of morbidity and mortality, and antibiotic prophylaxis greatly reduced the risk of infection from surgery.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!