Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Irreversible covalent modification

In mammalian cells, the two most common forms of covalent modification are partial proteolysis and ph osphorylation. Because cells lack the ability to reunite the two portions of a protein produced by hydrolysis of a peptide bond, proteolysis constitutes an irreversible modification. By contrast, phosphorylation is a reversible modification process. The phosphorylation of proteins on seryl, threonyl, or tyrosyl residues, catalyzed by protein kinases, is thermodynamically spontaneous. Equally spontaneous is the hydrolytic removal of these phosphoryl groups by enzymes called protein phosphatases. [Pg.76]

Mechanism-based inactivation results in formation of a covalent adduct between the active inhibitor and the enzyme, or between the active inhibitor and a substrate or cofactor molecule. If the mechanism involves covalent modification of the enzyme, then one should not be able to demonstrate a recovery of enzymatic activity after dialysis, gel filtration, ultrafiltration, or large dilution, as described in Chapters 5 to 7. Additionally, if the inactivation is covalent, denaturation of the enzyme should fail to release the inhibitory molecule into solution. If a radiolabeled version of the inactivator is available, one should be able to demonstrate irreversible association of radioactivity with the enzyme molecule even after denaturation and separation by gel filtration, and so on. In favorable cases one should likewise be able to demonstrate covalent association of the inhibitor with the enzyme by a combination of tryptic digestion and LC/MS methods. [Pg.230]

PAL has been known for 30 years, but a new era of applications has appeared recently through the evolution of more efficient photophores and activation, as well as new high-resolution separation and detection techniques. The photo-covalent modification of the binding site, which has an irreversible effect on activity and places a (radio)label, enables a multilevel analysis and identification on the biological target. [Pg.174]

The covalent modifications of histone tails such as acetylation, phosphorylation, and ubiquitination have been shown to be reversible. This reversibility help the cells to respond to these regulatory modifications and thereby, influence the gene expression. Methylation of histones however, has been considered to be a relatively stable and irreversible mark on histones. Nevertheless active turnover of methyl groups on histones do exist. One of the possible mechanism of removal of methyl... [Pg.400]

It is termed reversible, since the covalent modification that is catalysed by one enzyme is reversed by another enzyme. However, each individual reaction is irreversible. [Pg.48]

Histones within transcriptionally active chromatin and heterochromatin also differ in their patterns of covalent modification. The core histones of nucleosome particles (H2A, H2B, H3, H4 see Fig. 24-27) are modified by irreversible methylation of Lys residues, phosphorylation of Ser or Thr residues, acetylation (see below), or attachment of ubiquitin (see Fig. 27-41). Each of the core histones has two distinct structural domains. A central domain is involved in histone-histone interaction and the wrapping of DNA around the nucleosome. A second, lysine-rich amino-terminal domain is generally positioned near the exterior of the assembled nucleosome particle the covalent modifications occur at specific residues concentrated in this amino-terminal domain. The patterns of modification have led some researchers to propose the existence of a histone code, in which modification patterns are recognized by enzymes that alter the structure of chromatin. Modifications associated with transcriptional activation would be recognized by enzymes that make the chromatin more accessible to the transcription machinery. [Pg.1102]

The preceding experiments prove that there is an intermediate on the reaction pathway in each case, the measured rate constants for the formation and decay of the intermediate are at least as high as the value of kcat for the hydrolysis of the ester in the steady state. They do not, however, prove what the intermediate is. The evidence for covalent modification of Ser-195 of the enzyme stems from the early experiments on the irreversible inhibition of the enzyme by organo-phosphates such as diisopropyl fluorophosphate the inhibited protein was subjected to partial hydrolysis, and the peptide containing the phosphate ester was isolated and shown to be esterified on Ser-195.1516 The ultimate characterization of acylenzymes has come from x-ray diffraction studies of nonspecific acylenzymes at low pH, where they are stable (e.g., indolylacryloyl-chymotrypsin),17 and of specific acylenzymes at subzero temperatures and at low pH.18 When stable solutions of acylenzymes are restored to conditions under which they are unstable, they are found to react at the required rate. These experiments thus prove that the acylenzyme does occur on the reaction pathway. They do not rule out, however, the possibility that there are further intermediates. For example, they do not rule out an initial acylation on His-57 followed by rapid intramolecular transfer. Evidence concerning this and any other hypothetical intermediates must come from additional kinetic experiments and examination of the crystal structure of the enzyme. [Pg.122]

The reaction of an affinity label with an enzyme involves the initial formation of a reversibly bound enzyme-inhibitor complex followed by covalent modification and hence irreversible inhibition ... [Pg.476]

Partial Proteolysis Results in Irreversible Covalent Modifications... [Pg.175]

Partial proteolysis, an irreversible process, is used to activate proteases and other digestive enzymes after their secretion and to switch on enzymes that cause blood coagulation. Common types of reversible covalent modification include phosphorylation, adenylyla-tion, and disulfide reduction. [Pg.195]

This class of self-assembly incorporates elements from all of the preceeding classes and involved complex processes in which there are sequential steps involving self-assembly and covalent or irreversible modification. In general such processes are only found in biology at the present state of the field. [Pg.629]

Pyruvate kinase catalyzes the third irreversible step in glycolysis. It is activated by fructose 1,6-bisphosphate. ATP and the amino acid alanine allosterically inhibit the enzyme so that glycolysis slows when supplies of ATP and biosynthetic precursors (indicated by the levels of Ala) are already sufficiently high. In addition, in a control similar to that for PFK (see above), when the blood glucose concentration is low, glucagon is released and stimulates phosphorylation of the enzyme via a cAMP cascade (see Topic J7). This covalent modification inhibits the enzyme so that glycolysis slows down in times of low blood glucose levels. [Pg.288]

There are two general types of covalent modification of enzymes that regulate their activity. These are the irreversible activation of inactive enzyme precursors, the zymogens, and the reversible interconversion of active and inactive forms of an enzyme. [Pg.112]

The activity of enzymes (and indeed of the functionality of proteins in general) can be regulated by reversibly binding ligands (allosteric effectors) and by covalent modification (that can be either reversible or irreversible). [Pg.82]


See other pages where Irreversible covalent modification is mentioned: [Pg.155]    [Pg.155]    [Pg.464]    [Pg.76]    [Pg.167]    [Pg.127]    [Pg.127]    [Pg.215]    [Pg.222]    [Pg.227]    [Pg.640]    [Pg.330]    [Pg.46]    [Pg.325]    [Pg.274]    [Pg.267]    [Pg.31]    [Pg.225]    [Pg.13]    [Pg.474]    [Pg.135]    [Pg.433]    [Pg.437]    [Pg.635]    [Pg.638]    [Pg.358]    [Pg.392]    [Pg.258]    [Pg.107]    [Pg.15]    [Pg.80]    [Pg.83]    [Pg.84]   
See also in sourсe #XX -- [ Pg.76 , Pg.77 ]




SEARCH



Covalent modification

© 2024 chempedia.info