Three-dimensional structure of the bifunctional enzyme N-(5'-phosphoribosyl)anthranilate isomerase-indole-3-glycerol-phosphate synthase from Escherichia coli.

Priestle, John P.; Grütter, M.G.; White, Janice L.; Vincent, M. G.; Kania, Malgosia; Wilson, Eileen; Jardetzky, Theodore S.; Kirschner, Kasper; Jansonius, Johan N.

doi:10.1073/pnas.84.16.5690

Cited by 91 publications

(62 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The initial MIR model of this structure (Priestle et al, 1987) contained several misregistrations (residues 45-150) and other regions of poorly defined structure (residues 250-300, 350-400). All of these regions were detected using distance limits of 3.00-3.75 A , while the final model of the bifunctional enzyme (Wilmanns et al, 1992) behaved ideally (Fig.…”

Section: Resultsmentioning

confidence: 99%

Verification of protein structures: Patterns of nonbonded atomic interactions

1993

View full text Add to dashboard Cite

A novel method for differentiating between correctly and incorrectly determined regions of protein structures based on characteristic atomic interactions is described. Different types of atoms are distributed nonrandomly with respect to each other in proteins. Errors in model building lead to more randomized distributions of the different atom types, which can be distinguished from correct distributions by statistical methods.Atoms are classified in one of three categories: carbon (C), nitrogen (N), and oxygen (0). This leads to six different combinations of pairwise noncovalently bonded interactions (CC, CN, CO, NN, NO, and 00). A quadratic error function is used to characterize the set of pairwise interactions from nine-residue sliding windows in a database of 96 reliable protein structures. Regions of candidate protein structures that are mistraced or misregistered can then be identified by analysis of the pattern of nonbonded interactions from each window.

show abstract

Section: Resultsmentioning

confidence: 99%

Verification of protein structures: Patterns of nonbonded atomic interactions

1993

View full text Add to dashboard Cite

show abstract

“…The amino acid sequence alignment of IGP synthase from several organisms shows that identical amino acids are clustered within the carboxylterminal halves of the p-strands and the following loops [4]. The homology is particularly pronounced in the first P-strand-loop junction where Glu 53, Lys 55, Ala 57, Pro 59, Ser 60 and Gly 62 are 100% conserved.…”

Section: Resultsmentioning

confidence: 99%

“…Both biochemical and genetic studies have shown that the amino-terminal half of the protein catalyzes the IGP synthase reaction, whereas the carboxyl-terminal half is responsible for the PRA isomerase activity [l-3]. The crystal structure of the enzyme shows that the two activities reside on two well-separated domains [4]. Each domain has the folding pattern of triosephosphate isomerase [5], namely that of an 8-fold ,&Y barrel.…”

mentioning

confidence: 99%

“…More highly resolved structural information is necessary to propose a realistic mechanism for the catalytic process. However, the availability of 10 homologous amino acid sequences helps in identifying residues in the E. co/i sequence that are likely to be involved in catalysis [4]. Here, one of these, Lys 55, has been chosen for analysis by oligonucleotide-directed mutagenesis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Modification of a catalytically important residue of indoleglycerol‐phosphate synthase from Escherichia coli

Eberhard

Kirschner

1989

FEBS Letters

View full text Add to dashboard Cite

The active-site residues of indoleglycerol-phosphate synthase from Escherichia coli were tentatively localized by comparing crystallographic data with the amino acid identities among the known indoleglycerol-phosphate synthase sequences. To test the validity of the resulting model of catalysis one of the residues in the presumptive active site, Lys 55, was changed to serine using oligonucleotide-directed mutagenesis. The specificity constant k-,/K, of the mutant is 3 x l(Ptimes lower than that of the wild-type enzyme, due to a 60-fold decrease in k,, and a 450-fold increase in K,,,. This finding shows that Lys 55 is important for both catalysis and substrate binding.

show abstract

“…1). Also, despite the lack of detectable amino acid sequence similarity, HisA and TrpF belong to the same structural family of (␤␣) 8 -barrels (7,8), which is the most frequent fold among single-domain proteins (9). (␤␣) 8 -Barrel proteins consist of eight repeating units of ␤␣ modules.…”

Section: Nј-[(5ј-phosphoribosyl)formimino]-5-aminoimidazole-4-mentioning

confidence: 99%

Directed evolution of a (βα) ₈ -barrel enzyme to catalyze related reactions in two different metabolic pathways

Jürgens

Strom

Wegener

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

176

138

View full text Add to dashboard Cite

Enzymes participating in different metabolic pathways often have similar catalytic mechanisms and structures, suggesting their evolution from a common ancestral precursor enzyme. We sought to create a precursor-like enzyme for N -[(5 -phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (ProFAR) isomerase (HisA; EC 5.3.1.16) and phosphoribosylanthranilate (PRA) isomerase (TrpF; EC 5.3.1.24), which catalyze similar reactions in the biosynthesis of the amino acids histidine and tryptophan and have a similar (␤␣) 8-barrel structure. Using random mutagenesis and selection, we generated several HisA variants that catalyze the TrpF reaction both in vivo and in vitro, and one of these variants retained significant HisA activity. A more detailed analysis revealed that a single amino acid exchange could establish TrpF activity on the HisA scaffold. These findings suggest that HisA and TrpF may have evolved from an ancestral enzyme of broader substrate specificity and underscore that (␤␣) 8-barrel enzymes are very suitable for the design of new catalytic activities.E nzymes of contemporary metabolic pathways are generally specific and efficient biocatalysts. They can be categorized into a limited number of families, the members of which share similar reaction mechanisms, folds, or both (1). This leads to the idea that the members of a given enzyme family are evolutionarily related. In principle, two different evolutionary scenarios can be envisioned. New catalytic functions of enzymes could have evolved by changing the chemistry of catalysis, while retaining the binding capacity for a common ligand. This idea of retrograde evolution (2) was recently supported by the successful interconversion of the catalytic activity of two enzymes from tryptophan biosynthesis, which catalyze successive reactions in the pathway and therefore bind the same ligand (3). Alternatively, new catalytic functions could have evolved by retaining the chemistry of catalysis, while changing the substrate specificity (1). Along these lines, the patchwork model of enzyme evolution (4) postulates that ancestral enzymes were relatively unspecific and therefore were capable of catalyzing chemically similar reactions in different metabolic pathways. Genes encoding these enzymes would have duplicated in the course of evolution and would have subsequently specialized by diversification. NЈ-[(5Ј-Phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (ProFAR) isomerase (HisA; EC 5.3.1.16) and phosphoribosylanthranilate (PRA) isomerase (TrpF; EC 5.3.1.24) constitute a pair of similar enzymes, which are involved in the biosynthesis of the amino acids histidine and tryptophan, respectively (5, 6). Both HisA and TrpF catalyze an Amadori rearrangement, which is the irreversible isomerization of an aminoaldose to an aminoketose (Fig. 1). Also, despite the lack of detectable amino acid sequence similarity, HisA and TrpF belong to the same structural family of (␤␣) 8 -barrels (7, 8), which is the most frequent fold among single-dom...

show abstract

Three-dimensional structure of the bifunctional enzyme N-(5'-phosphoribosyl)anthranilate isomerase-indole-3-glycerol-phosphate synthase from Escherichia coli.

Cited by 91 publications

References 50 publications

Verification of protein structures: Patterns of nonbonded atomic interactions

Verification of protein structures: Patterns of nonbonded atomic interactions

Modification of a catalytically important residue of indoleglycerol‐phosphate synthase from Escherichia coli

Directed evolution of a (βα) ₈ -barrel enzyme to catalyze related reactions in two different metabolic pathways

Contact Info

Product

Resources

About

Three-dimensional structure of the bifunctional enzyme N-(5'-phosphoribosyl)anthranilate isomerase-indole-3-glycerol-phosphate synthase from Escherichia coli.

Cited by 91 publications

References 50 publications

Verification of protein structures: Patterns of nonbonded atomic interactions

Verification of protein structures: Patterns of nonbonded atomic interactions

Modification of a catalytically important residue of indoleglycerol‐phosphate synthase from Escherichia coli

Directed evolution of a (βα) 8 -barrel enzyme to catalyze related reactions in two different metabolic pathways

Contact Info

Product

Resources

About

Directed evolution of a (βα) ₈ -barrel enzyme to catalyze related reactions in two different metabolic pathways