Adenine and guanine nucleotides have been shown to exert multiple roles in central and peripheral nervous systems, and the sequential breakdown of these nucleotides by enzymatic systems is an important step in the modulation of their extracellular effects. The aim of this study was to investigate whether nucleotide hydrolysis also occurs in the cerebrospinal fluid (CSF) of rats. CSF was able to hydrolyze all guanine and adenine nucleotides investigated (2.0 mM): GDPz.Gt;ADP=ATP=GTPz.Gt;AMP=GMP. More detailed studies with the diphosphate nucleotides showed that the hydrolysis of ADP and GDP was linear with incubation time and protein concentration. The apparent K(M) (Henry-Michaelis-Menten constant) and V (maximal velocity) values for ADP and GDP were 164.3+/-54.7 microM and 12.2+/-3.8 nmol P(i)/min per mg protein, and 841.0+/-90.2 microM and 22.8+/-8.0 nmol P(i)/min per mg protein. The sum of ADP, GDP and UDP hydrolysis (2.0 mM) upon individual incubations with CSF was similar to the hydrolysis observed when all three nucleotides were incubated together. This pattern of hydrolysis strongly suggests the involvement of more than one enzyme activity. The higher maximum activity for GDP and UDP compared to ADP is compatible with presence of a soluble NTDPase5.
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http://dx.doi.org/10.1016/s0006-8993(02)02987-6 | DOI Listing |
J Chem Theory Comput
December 2024
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, and Translational Data Analytics Institute, The Ohio State University, Columbus, Ohio 43210, United States.
Polyphosphate nucleotides, such as ATP, ADP, GTP, and GDP, play a crucial role in modulating protein functions through binding and/or catalytically activating proteins (enzymes). However, accurately calculating the binding free energies for these charged and flexible ligands poses challenges due to slow conformational relaxation and the limitations of force fields. In this study, we examine the accuracy and reliability of alchemical free energy simulations with fixed-charge force fields for the binding of four nucleotides to nine proteins of various classes, including kinases, ATPases, and GTPases.
View Article and Find Full Text PDFOpen Biol
December 2024
Department of Medical Genetics, University Hospital of Reims, Reims, France.
J Cachexia Sarcopenia Muscle
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Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Background: Pathogenic variants in subunits of succinyl-CoA synthetase (SCS) are associated with mitochondrial encephalomyopathy in humans. SCS catalyses the conversion of succinyl-CoA to succinate coupled with substrate-level phosphorylation of either ADP or GDP in the TCA cycle. This report presents a muscle-specific conditional knock-out (KO) mouse model of Sucla2, the ADP-specific beta subunit of SCS, generating a novel in vivo model of mitochondrial myopathy.
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October 2024
Department of Chemistry, Universitat de les Illes Balears, Ctra. de Valldemossa, km. 7.5, 07122, Palma de Mallorca, Islas Baleares, Spain.
The Protein Data Bank (PDB) was scrutinized for the presence of noncovalent O ⋅ ⋅ ⋅ Al Triel Bonding (TrB) interactions, involving protein residues (e. g. GLU and GLN), adenosine/guanine diphosphate moieties (ADP and GDP), water molecules and two aluminum fluorides (AlF and AlF ).
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany.
Nucleoside diphosphate kinases (NDPKs) are encoded by genes and exist in various isoforms. Based on interactions with other proteins, they are involved in signal transduction, development and pathological processes such as tumorigenesis, metastasis and heart failure. In this study, we report a 1.
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