Phosphoribosyl anthranilate transferase

Biosynthesis Like other aromatic amino acids, e.g., Phe and Tyr, Trp is formed on the shikimic acid pathway. There is a branching point at chorismic acid one branch leads to Phe and Tyr, the other to Trp choris-mic acid - anthranilic acid (anthranilic acid synthase, EC 4.1.3.27)- A-(5 -0-phosphoribosyl)-anthranilic acid (anthranilic acid phosphoribosyl transferase, EC 2.4.2.18)- 1 -o-carboxyphenylamino-1 -deoxyribu-lose 5-phosphate [A-(5 -phosphoribosyl)anthranilic acid isomerase]- indole-3-glycerol phosphate (in-dole-3-glycerol phosphate synthase, EC 4.1.1.48) - indole (tryptophan synthase, EC 4.2.1,20)+serine - Trp. Many biologically active indole compounds are derived from Trp, e. g., 5-hydroxytryptophan, 5-hydroxy-tryptamine ( serotonin), and melatonin as well as many indole alkaloids. 

The second step in the tryptophan branch, the conversion of anthranilate toN-phosphoribosyl anthranilate [Fig. 4 (14)], involves the addition of phos-phoribosyl moiety of 5-phosphoribosyl- 1-pyrophosphate to the C-3 position of anthranilate, catalyzed by anthranilate phosphoribosyltransferase (PRT). Maximum activity of the transferase appears to require both 5-phosphoribosyl pyrophosphate and MgCl2 for maximum activity. Certain members of the enteric bacteria have the enzymes catalyzing the first and second steps of this sequence aggregated into a single complex (Largen and Belser, 1975). However, this situation does not appear to be true in any other organisms studied (Hankins et al., 1976). 

The second enzyme of the pathway leading to tryptophan, 5-phosphoribosyl-pyrophosphate transferase (PR transferase), causes addition of a phosphoribosyl unit (12) to anthranilic acid. An additional series of enzymes then brings about a rearrangement and the ultimate formation of indoleglycerol 3-phosphate (13). 

Biosynthetic processes Elongation of RNA or DNA chains Other synthetic routes RNA polymerase I DNA polymerase Poly(ADP-ribose)polymerase Carbamoyl phosphate synthetase Anthranilate synthase-phosphoribosyl transferase Glycogen synthetase Methionyl-tRNA synthetase ATP phosphoribosyl transferase Zn2+... 

The next enzyme in the tryptophan pathway is anthranilate-5-phosphoribosyl transferase (EC 2.4.2.18). In some microbial enzymes it is part of the AS enzyme complex, but this transferase activity could not be measured in the purified C. roseus enzyme. 

Anthranilate phosphoribosyl transferase (EC 2.4.2.18) (AnPRT) belongs to the class of transferase enzyme, which enacts the transfer of specific functional group (e.g., methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). It transfer a ribose group between the basic functional group of anthranilate and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP). AnPRT has four domains and its quaternary structure consists of two identical protein structures [13]. Each domain of AnPRT contains a magnesium ion and a pyrophosphate molecule as the active site. The secondary structure of AnPRT consists mainly of alpha helices with a beta sheet within each domain (Fig. 14.6). 

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