Classes synthetase

There are two classes of synthetase, each with 10 members. The amino acid sequences of these two classes have regions which are identical for all enzymes of the particular class (Eriani, 1990). The class 1 synthetases acylate the tRNA at the 2 -hydroxyl of the terminal adenosine, while the class 2 enzymes acylate predominantly at the 3 -function of the ribose. 

The close connection of this enzyme family with the transfer of genetic information has made it a popular object of study when dealing with questions regarding the formation and evolution of the genetic code (see Sect. 8.1). It is now agreed that the aminoacyl-tRNA synthetases are a very ancient enzyme species which do not, however, arise from one single primeval enzyme, but from at least two, corresponding to the synthetase classes. 

An important factor in the evolution of the genetic code is certainly provided by the aminoacyl-tRNA synthetases (see Sect. 5.3.2). It is clear that the two synthetase classes are not randomly distributed across the matrix of the amino acid assignment of the genetic code. For example, with one exception, all XUX codons code for class 1 synthetases, while all XCX codons code for class 2 aminoacyl-tRNA synthetases. A possible explanation could be that the synthetases and the genetic code evolved simultaneously. However, it is more likely that these enzymes evolved when the genetic code had already been established (Wetzel, 1995). 

Beyer, D., Kroll, H. P., Endermann, R., Schiller, G., Siegel, S., Bauser, M., Pohlmann, J., Brands, M., Ziegelbauer, K., Haebich, D., Eymann, C., and Brotz-Oesterhelt, H. (2004). New class of bacterial phenylalanyl-tRNA synthetase inhibitors with high potency and broad-spectrum activity. Antimicrob. Agents Chemother. 48, 525—532. 

Figure 1 Overview of specific use of seienium in bioiogical systems. Selenium can be incorporated into macromolecules in at least three separate pathways. From the reduced form of selenide, selenium is activated to selenophosphate by the action of the enzyme selenophosphate synthetase (SPS or SelD). This activated form is then used as a substrate for pathway-specific enzymes that lead to (1) insertion as selenocysteine into proteins during translation (selenoproteins), (2) incorporation into tRNA molecules as mnm Se U or Se U, and (3) insertion into a unique class of molybdoenzymes as a labile, but required, cofactor. The need for activation to selenophosphate has been demonstrated in all cases at the genetic and biochemical level, with the exception of the labile selenoenzymes, where activation of selenium has only been proposed based on proximity of genes within an operon encoding SPS and a molybdoenzyme. ...

Phosphopantetheine tethering is a posttranslational modification that takes place on the active site serine of carrier proteins - acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs), also termed thiolation (T) domains - during the biosynthesis of fatty acids (FAs) (use ACPs) (Scheme 23), polyketides (PKs) (use ACPs) (Scheme 24), and nonribosomal peptides (NRPs) (use T domain) (Scheme 25). It is only after the covalent attachment of the 20-A Ppant arm, required for facile transfer of the various building block constituents of the molecules to be formed, that the carrier proteins can interact with the other components of the different multi-modular assembly lines (fatty acid synthases (FASs), polyketide synthases (PKSs), and nonribosomal peptide synthetases (NRPSs)) on which the compounds of interest are assembled. The structural organizations of FASs, PKSs, and NRPSs are analogous and can be divided into three broad classes the types I, II, and III systems. Even though the role of the carrier proteins is the same in all systems, their mode of action differs from one system to another. In the type I systems the carrier proteins usually only interact in cis with domains to which they are physically attached, with the exception of the PPTases and external type II thioesterase (TEII) domains that act in trans. In the type II systems the carrier proteins selectively interact... 

Introduction Peptide-Based Natural Products Nonribosomal Peptide Natural Products The Canonical Enzymology of NRPS Modules Classes of Nonribosomal Peptide Synthetases... 

The ligation reactions catalyzed by ligases ( synthetases, class 6) are energy-dependent and are therefore always coupled to the hydrolysis of nucleoside triphosphates. 

A major class of enzymes, also referred to as synthetases, that catalyze the joining of two entities with the concomitant hydrolysis of molecules such as ATP or GTP. 

The structures of all the aminoacyl-tRNA synthetases of E. coli have been determined. Researchers have divided them into two classes (Table 27-7) based on substantial differences in primary and tertiary structure and in reaction mechanism (Fig. 27-14) these two classes are the same in all organisms. There is no evidence for a common ancestor, and the biological, chemical, or evolutionary reasons for two enzyme classes for essentially identical processes remain obscure. 

MECHANISM FIGURE 27-14 Aminoacylation of tRNA by aminoacyl-tRNA synthetases. Step is formation of an aminoacyl adenylate, which remains bound to the active site. In the second step the aminoacyl group is transferred to the tRNA. The mechanism of this step is somewhat different for the two classes of aminoacyl-tRNA synthetases (see Table 27-7). For class I enzymes, (2a) the aminoacyl group is transferred initially to the 2 -hydroxyl group of the 3 -terminal A residue, then (3a) to the 3 -hydroxyl group by a transesterification reaction. For class II enzymes, ( the... 

Class II aminoacyl-tRNA synthetases contain a different set of three "signature sequences," two of which form an ATP-binding catalytic domain. The active site structure is built on an antiparallel (3 sheet and is surrounded by two helices (Fig. 29-9). Each class contains subgroups with inserted loops that form other domains. In the following tabulation the reference numbers refer to three-dimensional structural studies. 

Mechanisms of reaction. Activation of an amino acid occurs by a direct in-line nucleophilic displacement by a carboxylate oxygen atom of the amino acid on the a phosphorus atom of MgATP to form the aminoacyl adenylate (Eq. 29-1, step a). For yeast phenylalanyl-tRNA synthetases the preferred form of MgATP appears to be the P,y-bidentate (A screw sense) complex (p. 643).250 This is followed by a second nucleophilic displacement, this one on the C = 0 group of the aminoacyl adenylate by the -OH group of the tRNA (Eq. 29-1, step b Fig. 29-9C). A conformational change in the protein may be required to permit dissociation of the product, the aminoacyl-tRNA. In the complex of a class I synthetase with aminoacyl... 

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