The relationships between release of (3)H-labeled lipoyl moieties by trypsin and lipoamidase and accompanying loss of overall enzymatic activity of the Escherichia coli pyruvate and alpha-ketoglutarate dehydrogenase complexes were studied. Trypsin releases lipoyl domains together with their covalently attached lipoyl moieties from the "inner" core of the dihydrolipoyl transacetylase and the dihydrolipoyl transsuccinylase whereas lipoamidase releases only the lipoyl moieties. The results show that release of lipoyl domains by trypsin and release of lipoyl moieties by lipoamidase proceeded at faster rates than the accompanying loss of overall activity of the two complexes. Trypsin released about half of the lipoyl domains in the pyruvate dehydrogenase complex without significant effect on the overall activity. A model is presented to explain these and other observations on active-site coupling via lipoyl moieties.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/bi00519a007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NMN partially rescues cuproptosis by upregulating sirt2 to increase intracellular NADPH.
Sci Rep
August 2024
School of Public Health, Hangzhou Normal University, Hangzhou, China.
Cuproptosis is characterized by lipoylated protein aggregation and loss of iron-sulfur (Fe-S) proteins, which are crucial for a wide range of important cellular functions, including DNA replication and damage repair. Sirt2 and sirt4 are lipoamidases that remove the lipoyl moiety from lipoylated proteins using nicotinamide adenine dinucleotide (NAD) as a cofactor. However, to date, it is not clear whether nicotinamide mononucleotide (NMN), a precursor of NAD, affects cellular sensitivity to cuproptosis.
View Article and Find Full Text PDFAntitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex.
J Med Chem
May 2024
College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, P. R. China.
Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh) (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy and by specifically targeting mitochondria instigating mitochondrial dysfunction.
View Article and Find Full Text PDFStructures and comparison of endogenous 2-oxoglutarate and pyruvate dehydrogenase complexes from bovine kidney.
Cell Discov
November 2022
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
The α-keto acid dehydrogenase complex family catalyzes the essential oxidative decarboxylation of α-keto acids to yield acyl-CoA and NADH. Despite performing the same overarching reaction, members of the family have different component structures and structural organization between each other and across phylogenetic species. While native structures of α-keto acid dehydrogenase complexes from bacteria and fungi became available recently, the atomic structure and organization of their mammalian counterparts in native states remain unknown.
View Article and Find Full Text PDFIn Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1.
ACS Bio Med Chem Au
October 2022
Department of Chemistry and Biochemistry and Molecular Biology and the Howard Hughes Medical Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Lipoyl synthase (LS) catalyzes the last step in the biosynthesis of the lipoyl cofactor, which is the attachment of sulfur atoms at C6 and C8 of an -octanoyllysyl side chain of a lipoyl carrier protein (LCP). The protein is a member of the radical -adenosylmethionine (SAM) superfamily of enzymes, which use SAM as a precursor to a 5'-deoxyadenosyl 5'-radical (5'-dA·). The role of the 5'-dA· in the LS reaction is to abstract hydrogen atoms from C6 and C8 of the octanoyl moiety of the substrate to initiate subsequent sulfur attachment.
View Article and Find Full Text PDFPalmitoylation of Voltage-Gated Ion Channels.
Int J Mol Sci
August 2022
Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, Spain.
Protein lipidation is one of the most common forms of posttranslational modification. This alteration couples different lipids, such as fatty acids, phospho- and glycolipids and sterols, to cellular proteins. Lipidation regulates different aspects of the protein's physiology, including structure, stability and affinity for cellular membranes and protein-protein interactions.
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!