Bonds isopeptide

Small tfbiquitin-like modifier represents a family of evolutionary conserved proteins that are distantly related in amino-acid sequence to ubiquitin, but share the same structural folding with ubiquitin proteins. SUMO proteins are covalently conjugated to protein substrates by an isopeptide bond through their carboxyl termini. SUMO addition to lysine residues of target proteins, termed SUMOylation, mediates post-transla-tional modification and requires a set of enzymes that are distinct from those that act on ubiquitin. SUMOylation regulates the activity of a variety of tar get proteins including transcription factors. 

Small Ubiquitin-like modifier (SUMO) is a conserved protein that is ubiquitously expressed in eukaryotes and is essential for viability. It serves as a reversible posttranslational modifier by forming an isopeptide bond with lysine residues in many target proteins, in a catalytic process termed SUMOylation. SUMOylation of proteins results in altered inter- or intramolecular interactions of the modified target (Fig. 1). 

Modification by SUMO is a reversible and often highly dynamic process. Cleavage of the isopeptide bond between SUMO and its targets is accomplished by SUMO specific cysteine proteases of the Ulp/SENP family (Fig. 2). Six members were identified in humans,... 

The transglutaminases are calcium-dependent enzymes that catalyse the cross-linking of proteins by promoting the formation of isopeptide bonds between the /-carboxyl group of a glutamine in one polypeptide chain and the e-amino group of a lysine in the second (Greenberg et al., 1991). These... 

The amide bonds in peptides are usually called peptide bonds, and they are formed between C(l) of one amino acid and N(2) of another (sometimes called eupeptide bonds). Peptides may also include compounds linked by other amide bonds (sometimes called isopeptide bonds). 

UCHs are cysteine proteases in that the critical residue in the catalytic site is a cysteine. In addition, histidine and aspartate residues are critical for catalytic activity. All UCHs contain these residues even if they do not share a high degree of homology elsewhere in the sequence. For example, the Aplysia UCH (Ap-uch) critical for the induction oflong-term facilitation has only 39% homology to its human counterpart UCH-Lf. Ap-uch and UCH-Ll both contain the catalytic cysteine, histidine, and aspartate residues at similar positions in the molecule. UCHs cleave small peptide chains linked to the C-terminus of ubiquitin. UBPs can cleave the isopeptide bond between ubiquitins in a polyubiquitin chain and the isopeptide bond between the ubiquitin and the substrate. 

Heating of foods rich in proteins may lead to formation of crosslinking isopeptide bonds between the S-NH2 group of lysine and the p- and y-carboxyl groups of aspartic and glutamic acid residues or their amides. 

These enzymes [EC 6.3.2.19] catalyze the reaction of ATP with ubiquitin and a lysyl residue in a protein to produce a protein containing an iV-ubiquityllysyl residue, AMP, and pyrophosphate (or, diphosphate). Ubiquitin is coupled to the protein by an isopeptide bond between the C-terminal glycine of ubiquitin and -amino groups of lysyl residues in the protein. An intermediate in the reaction contains one ubiquitin residue bound as a thi-olester to the enzyme, and a residue of ubiquitin adenylate noncovalently bound to the enzyme. 

The isopeptide bond between Ub and other proteins can be hydrolyzed there are multiple, ATP-independent proteases (the yeast Saccharomyces cerevisiae has at least 20 of them) whose common property is the ability to recognize Ub moiety and cleave at the Ub-adduct junction. One cause of the striking multiplicity of these deubiquitylating enzymes (DUBs) (17) is the diversity of their targets, which include linear (DNA-encoded) Ub fusions, Ub adducts with small nucleophiles such as glutathione, and also free and substrate-linked multi-Ub chains. 

Fig. 1. A schematic diagram outlining the hierarchic structure of the ubiquitin system. In an ATP-dependent manner a thioester bond is formed between the C-terminus of ubiquitin and an internal cystein residue of the ubiquitin-activating enzyme. Subsequently, ubiquitin is transferred to a member of the family of ubiquitin-conjugating enzymes, which are also able to form a thioester bond with ubiquitin. The third class of enzymes, the ubiquitin ligases, direct ubiquitin to the proteolytic substrates. Different families of this class of enzymes are known, some of which are also able to form a thioester intermediate with ubiquitin (HECT-domain ligases). The final ubiquitin-substrate linkage is an isopeptide bond between the C-terminus of ubiquitin and internal lysine residues in the substrate proteins...

A peptide is any compound produced by amide formation between a carboxyl group of one amino acid and an amino group of another. The amide bonds in peptides are called peptide bonds. The word peptide is usually applied to compounds whose amide bonds (sometimes called eupeptide bonds) are formed between C-1 of one amino acid and N-2 of another, but it includes compounds with residues linked by other amide bonds (sometimes called isopeptide bonds). Peptides with fewer than about 10-20 residues may also be called oligopeptides those with more residues are called polypeptides. Polypeptides of specific sequence of more than about 50 residues are usually known as proteins, but authors differ greatly on where they start to apply this term. 

FIGURE 27-41 Three-step cascade pathway by which ubiquitin is attached to a protein. Two different enzyme-ubiquitin intermediates are involved. The free carboxyl group of ubiquitin s carboxyl-terminal Gly residue is ultimately linked through an amide (isopeptide) bond to an e-amino group of a Lys residue of the target protein. Additional cycles produce polyubiquitin, a covalent polymer of ubiquitin subunits that targets the attached protein for destruction in eukaryotes. 

Fig. 1. Basic scheme of fibrin polymerization and fibrinolysis. The clot is formed on the conversion of fibrinogen to fibrin by cleavage of the fibrinopeptides by thrombin, followed by stabilization of the network with isopeptide bonds by the transglutaminase Factor XHIa. The clot is dissolved through proteolysis by the enzyme plasmin, which is activated on the fibrin surface by plasminogen activators. This process is controlled by several inhibitory reactions (black arrows).

Fig. 8. Formation of isopeptide bond catalyzed by Factor XHIa. The chemical reaction was catalyzed by Factor XHIa, yielding insoluble fibrin crosslinked by Ne-(7 glutamyl) lysine bonds. Factor XIII is activated to Factor XHIa by thrombin in the presence of calcium ions and fibrin.

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