3506-25-0Relevant articles and documents
Glutamates 78 and 122 in the Active Site of Saccharopine Dehydrogenase Contribute to Reactant Binding and Modulate the Basicity of the Acid-Base Catalysts
Ekanayake, Devi K.,Andi, Babak,Bobyk, Kostyantyn D.,West, Ann H.,Cook, Paul F.
, p. 20756 - 20768 (2010)
Saccharopine dehydrogenase catalyzes the NAD-dependent oxidative deamination of saccharopine to give L-lysine and α-ketoglutarate. There are a number of conserved hydrophilic, ionizable residues in the active site, all of which must be important to the overall reaction. In an attempt to determine the contribution to binding and rate enhancement of each of the residues in the active site, mutations at each residue are being made, and double mutants are being made to estimate the interrelationship between residues. Here, we report the effects of mutations of active site glutamate residues, Glu78 and Glu122, on reactant binding and catalysis. Site-directed mutagenesis was used to generate E78Q, E122Q, E78Q/E122Q, E78A, E122A, and E78A/E122A mutant enzymes. Mutation of these residues increases the positive charge of the active site and is expected to affect the pKa values of the catalytic groups. Each mutant enzyme was completely characterized with respect to its kinetic and chemical mechanism. The kinetic mechanism remains the same as that of wild type enzymes for all of the mutant enzymes, with the exception of E78A, which exhibits binding of α-ketoglutarate to E and E·NADH. Large changes in V/K Lys, but not V, suggest that Glu78 and Glu122 contribute binding energy for lysine. Shifts of more than a pH unit to higher and lower pH of the pKa values observed in the V/KLys pH-rate profile of the mutant enzymes suggests that the presence of Glu78 and Glu122 modulates the basicity of the catalytic groups.
Synthesis of monolysyl advanced glycation endproducts and their incorporation into collagen model peptides
Woods, Tom M.,Kamalov, Meder,Harris, Paul W. R.,Cooper, Garth J. S.,Brimble, Margaret
, p. 5740 - 5743 (2012)
The synthesis of advanced glycation endproducts (AGEs), CML, CEL, and pyrraline and their incorporation into collagen model peptides is reported. AGEs are modified amino acids that form on proteins such as collagen and are thought to play a significant role in the pathogenesis of many diseases, particularly diabetes. The synthesis and incorporation of these compounds into synthetic peptides is a key step in developing model systems with which to investigate AGE-modified proteins.
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Leclerc,J.,Benoiton,L.
, p. 1047 - 1051 (1968)
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Selection and breeding of lysine-accumulating Saccharomyces cerevisiae as a stable source of lysine in the rumen
Ohsumi,Sato,Yoshihara,Ikeda
, p. 1302 - 1305 (1994)
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Kearley,Ingersoll
, p. 5783,5785 (1951)
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Trimethylsilyl Trifluoromethanesulphonate as a Useful Deprotecting Reagent in Both Solution and Solid Phase Peptide Syntheses
Fujii, Nobutaka,Otaka, Akira,Ikemura, Osamu,Akaji, Kenichi,Funakoshi, Susumu,et al.
, p. 274 - 275 (1987)
Trimethylsilyl trifluoromethanesulphonate in trifluoroacetic acid has been found to cleave, in the presence of thioaisole, a number of protecting groups currently employed in peptide synthesis, without significant side reactions and with a much faster rate of reaction than trifluoromethanesulphonic acid in trifluoroacetic acid; this new deprotecting reagent has been used in solution and solid phase peptide syntheses of neuromedin U-25 (a 25-residue peptide) and a rabbit stomach peptide (an 8-residue peptide), respectively.
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Berg
, p. 9,12 (1936)
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DISCOVERY, TOTAL SYNTHESIS, AND BIOACTIVITY OF DOSCADENAMIDES
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Page/Page column 81; 84-85, (2021/02/05)
The invention is directed towards compounds (e.g., Formulae (I)-(IX)), their mechanism of action, processes to prepare the compounds, methods of activating quorum sensing signaling activity, and methods of treating diseases and disorders using the compounds described herein (e.g., Formulae (I)-(IX)).
Development of a Raltegravir-based Photoaffinity-Labeled Probe for Human Immunodeficiency Virus-1 Integrase Capture
Pala, Nicolino,Esposito, Francesca,Tramontano, Enzo,Singh, Pankaj Kumar,Sanna, Vanna,Carcelli, Mauro,Haigh, Lisa D.,Satta, Sandro,Sechi, Mario
supporting information, p. 1986 - 1992 (2020/11/09)
Photoaffinity labeling (PAL) is one of the upcoming and powerful tools in the field of molecular recognition. It includes the determination of dynamic parameters, such as the identification and localization of the target protein and the site of drug binding. In this study, a photoaffinity-labeled probe for full-length human immunodeficiency virus-1 integrase (HIV-1 IN) capture was designed and synthesized, following the structure of the FDA-approved drug Raltegravir. This photoprobe was found to retain the HIV IN inhibitory potential in comparison with its parent molecule and demonstrates the ability to label the HIV-1 IN protein. Putative photoprobe/inhibitor binding sites near the catalytic site were then identified after protein digestion coupled to mass and molecular modeling analyses.
