4WUI

Crystal structure of TrpF from Jonesia denitrificans

Summary for 4WUI

• Entry DOI: 10.2210/pdb4wui/pdb
• Descriptor: N-(5'-phosphoribosyl)anthranilate isomerase, CITRIC ACID (3 entities in total)
• Functional Keywords: tim-barrel, isomerase, tryptophan synthesis, structural genomics, psi-biology, midwest center for structural genomics, mcsg
• Biological source: Jonesia denitrificans
• Total number of polymer chains: 1
• Total formula weight: 22007.40

Authors

Michalska, K.,Verduzco-Castro, E.A.,Endres, M.,Barona-Gomez, F.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2014-10-31, release date: 2014-11-26, Last modification date: 2023-12-27)

Primary citation

Verduzco-Castro, E.A.,Michalska, K.,Endres, M.,Juarez-Vazquez, A.L.,Noda-Garcia, L.,Chang, C.,Henry, C.S.,Babnigg, G.,Joachimiak, A.,Barona-Gomez, F.
Co-occurrence of analogous enzymes determines evolution of a novel ( beta alpha )8-isomerase sub-family after non-conserved mutations in flexible loop.
Biochem. J., 473:1141-1152, 2016

PubMed Abstract: We investigate the evolution of co-occurring analogous enzymes involved in L-tryptophan and L-histidine biosynthesis in Actinobacteria Phylogenetic analysis of trpF homologues, a missing gene in certain clades of this lineage whose absence is complemented by a dual-substrate HisA homologue, termed PriA, found that they fall into three categories: (i) trpF-1, an L-tryptophan biosynthetic gene horizontally acquired by certain Corynebacterium species; (ii) trpF-2, a paralogue known to be involved in synthesizing a pyrrolopyrrole moiety and (iii) trpF-3, a variable non-conserved orthologue of trpF-1 We previously investigated the effect of trpF-1 upon the evolution of PriA substrate specificity, but nothing is known about the relationship between trpF-3 and priA After in vitro steady-state enzyme kinetics we found that trpF-3 encodes a phosphoribosyl anthranilate isomerase. However, mutation of this gene in Streptomyces sviceus did not lead to auxothrophy, as expected from the biosynthetic role of trpF-1 Biochemical characterization of a dozen co-occurring TrpF-2 or TrpF-3, with PriA homologues, explained the prototrophic phenotype, and unveiled an enzyme activity trade-off between TrpF and PriA. X-ray structural analysis suggests that the function of these PriA homologues is mediated by non-conserved mutations in the flexible L5 loop, which may be responsible for different substrate affinities. Thus, the PriA homologues that co-occur with TrpF-3 represent a novel enzyme family, termed PriB, which evolved in response to PRA isomerase activity. The characterization of co-occurring enzymes provides insights into the influence of functional redundancy on the evolution of enzyme function, which could be useful for enzyme functional annotation.

PubMed: 26929404
DOI: 10.1042/BJ20151271

Experimental method

X-RAY DIFFRACTION (1.09 Å)