Publications

• The structures of anthranilate synthase of Serratia marcescens crystallized in the presence of (i) its substrates, chorismate and glutamine, and a product, glutamate, and (ii) its end-product inhibitor, L-tryptophan.

  Spraggon G., Kim C., Nguyen-Huu X., Yee M.-C., Yanofsky C., Mills S.E.

  The crystal structure of anthranilate synthase (AS) from Serratia marcescens, a mesophilic bacterium, has been solved in the presence of its substrates, chorismate and glutamine, and one product, glutamate, at 1.95 A, and with its bound feedback inhibitor, tryptophan, at 2.4 A. In comparison with ... >> More

  The crystal structure of anthranilate synthase (AS) from Serratia marcescens, a mesophilic bacterium, has been solved in the presence of its substrates, chorismate and glutamine, and one product, glutamate, at 1.95 A, and with its bound feedback inhibitor, tryptophan, at 2.4 A. In comparison with the AS structure from the hyperthermophile Sulfolobus solfataricus, the S. marcescens structure shows similar subunit structures but a markedly different oligomeric organization. One crystal form of the S. marcescens enzyme displays a bound pyruvate as well as a putative anthranilate (the nitrogen group is ambiguous) in the TrpE subunit. It also confirms the presence of a covalently bound glutamyl thioester intermediate in the TrpG subunit. The tryptophan-bound form reveals that the inhibitor binds at a site distinct from that of the substrate, chorismate. Bound tryptophan appears to prevent chorismate binding by a demonstrable conformational effect, and the structure reveals how occupancy of only one of the two feedback inhibition sites can immobilize the catalytic activity of both TrpE subunits. The presence of effectors in the structure provides a view of the locations of some of the amino acid residues in the active sites. Our findings are discussed in terms of the previously described AS structure of S. solfataricus, mutational data obtained from enteric bacteria, and the enzyme's mechanism of action. << Less

  Proc. Natl. Acad. Sci. U.S.A. 98:6021-6026(2001) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Characterization of composite aminodeoxyisochorismate synthase and aminodeoxyisochorismate lyase activities of anthranilate synthase.

  Morollo A.A., Bauerle R.

  Anthranilate synthase [chorismate pyruvatelyase (amino-accepting), E.C.4.1.3.27] catalyzes the formation of anthranilate (o-aminobenzoate) and pyruvic acid from chorismate and glutamine. A mutant form of the enzyme from Salmonella typhimurium accumulates a compound that we had isolated and identif ... >> More

  Anthranilate synthase [chorismate pyruvatelyase (amino-accepting), E.C.4.1.3.27] catalyzes the formation of anthranilate (o-aminobenzoate) and pyruvic acid from chorismate and glutamine. A mutant form of the enzyme from Salmonella typhimurium accumulates a compound that we had isolated and identified as trans-6-amino-5-[(1-carboxyethenyl)-oxy]-1,3-cyclohexadiene-1-carboxylic acid, commonly called aminodeoxyisochorismate (ADIC). Here we report that ADIC is formed by a reversible, Mg(2+)-dependent ADIC synthase activity of anthranilate synthase that can be functionally uncoupled from a Mg(2+)-dependent ADIC lyase activity of the enzyme by single amino acid substitutions in the TrpE subunit of the anthranilate synthase complex of S. typhimurium. Both of the component activities of the enzyme are sensitive to feedback inhibition by L-tryptophan. Purified ADIC is quantitatively converted to anthranilate and pyruvic acid by the ADIC lyase activity of wild-type anthranilate synthase. ADIC also serves as a substrate for the formation of chorismate by the enzyme in the absence of glutamine and (NH4)2SO4. The rate of ADIC formation by the mutant enzyme and the steady-state parameters for ADIC utilization by the wild-type enzyme are consistent with a role for ADIC as an enzyme-bound intermediate that does not accumulate during the course of the anthranilate synthase reaction. The altered catalytic specificity of mutant anthranilate synthase enzymes suggests a potential role for ADIC in secondary metabolism. << Less

  Proc Natl Acad Sci U S A 90:9983-9987(1993) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.