C-N ligase

Since the ribosomal peptidyltransferase activity is not suitable for practical use as a simple C - N ligase and, in addition, the multienzyme complexes involved in bacterial peptide synthesis[S] do not seem to possess a general applicability, only the reverse catalytic potential of peptidases can be considered as valuable supplement to chemical coupling methods (cf. Sect. 12.5.3). In addition, peptidases have been used successfully for enzymatic manipulation of protecting groups in peptide synthesis 7-9 . 

Formation of these amino acid conjugates is catalysed by p-(9-cytokinin)-aIanine synthase, classified as C-N ligase, and characterised in lupin seeds [134]. The enzyme requires O-acetylserine as donor of the alanine moiety and recognises all main cytokinin bases (including BA) and many other purine derivatives as substrates. Similarly to cytokinin 7- and 9-glucosides, also cytokinin 9-alanyl derivatives are biologically inactive and metabolically stable, and are therefore candidates to be cytokinin-inactivation and detoxification products. 

Substrate binding at the active site [8] plays a crucial role in protease-catalyzed peptide bond formation. Unfortunately, a simple C-N ligase is not capable of developing different substrate binding regions, for example by induced fit, for the structurally diverse amino acid side chain functionalities. According to Linus Pauling the action of an enzyme depends on the complementarity of the active site to the transition state structure of a reaction, as shown in Scheme 2 for peptide bond formation. 

Ligases Formation-cleavage of C-O, C-S, C-N, and C-C bonds with triphosphate cleavage... 

Class 6. Ligases join two separate molecules by creating a new chemical bond at the expense of nucleoside triphosphate (e.g., ATP) hydrolysis. They include enzymes that form C-O, C-S, C-N, and C-C bonds. Synthetases are ligases. 

Ligase reactions provide remarkable examples of enzyme-catalyzed reactions with 6 to 8 reactants. Since C = N -R at specified pH and C = Af"- "at specified pH and specified availability of oxygen atoms, this means there are 5 to 7 components. Three or four conservation equations are provided by elements, and so these enzyme mechanisms introduce 2 to 4 or 1 to 3 conservation equations in addition in coupling. In this respect enzyme-catalyzed reactions can be very different from chemical reactions (see Chapter 7). 

Ligases - These mediate C-0, C-S, C-N, and C-C bond formation. Phosphate bond-forming enzymes have been used most widely. Coenzyme A is conveniently made, using a polyacrylamide-supported synthetase to couple ATP and pan-tethine.53 The use of phosphorylases has also solved some severe... 

C/N] Nedd4 WWII, domain of rat ubiquitin ligase complexed with EnaC P2 peptide 48+15 22 212... 

Chakravarty, P.K., Greenlee, W.J., Parsons, W.H., Patchett, A.A., Combs, P, Roth, A., Busch, R.D., and Mellin, T.N., (3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine. c-Alanine ligase, J. Med. Chem., 32, 1886, 1989. 

Ligases split C-C, C-O, C-N, C-S, and C-halogen bonds without hydrolysis or oxidation, mostly with the concomitant consumption of high-energy compounds like adenosine triphosphate (ATP) and other nucleoside triphosphates. 

Ligases are enzymes that catalyze a reaction in which a C—C, C—S, C—O, or C—N bond is made or broken. This is accompanied by an ATP-ADP interconversion. For example, DNA ligase catalyzes the joining of the hydroxyl group of a nucleotide in a DNA strand with the phosphoryl group of the adjacent nucleotide to form a phos-phoester bond ... 

EC 6 Ligases Formation of C-O-, C-S-, C-N-, C-C-bonds two-substrate reactions co-substrate ATP required... 

Ligases Formation of C—O, C—S, C—N, and phosphoryl bonds very important in molecular biology... 

Ligases Formation of C-C, C-S, C-0, and C-N bonds by condensation reactions, coupled to hydrolysis of ATP (adenosine triphosphate)... 

Forming C—0 bonds 6.1.1 Aminoacid-RNA ligases 6.3 Forming C—N bonds Amino-acid activating enzyme VII-8... 

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Proteins with destabilizing N-terminal residues such as arginine and leucine are recognized by a RING-type ubiquitin ligase (termed N-recognin or E3-a) that, together with a specific ubiquitin c, mediates poly-ubiquitylation. 

The third type of E3 ligases is represented by the polycomb protein 2 (Pc2), which was reported to enhance sumoylation of the substrate CtBP. N- and C-terminal domains in Pc2 that have been implicated in CtBP sumoylation do not resemble known E3 ligases. Like RanBP2, Pc2 expression is restricted to higher eukaryotes. 

Zheng, N., et al.. Structure of a c-Cbl-UbcH7 complex RING domain function in ubiquitin-protein ligases. Cell, 2000, 102(4), 533-9. 

Bays, N. W., Gardner, R. G., Seelig, L. P., JoAZEiRO, C. A., and Hampton, R. Y. Hrdlp/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nature Cell Biol. 2000, 3, 24-29. 

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