4wui | pdb_00004wui
Crystal structure of TrpF from Jonesia denitrificans
Structural highlights
Publication Abstract from PubMedWe 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. Co-occurrence of analogous enzymes determines evolution of a novel (betaalpha)8-isomerase sub-family after non-conserved mutations in flexible loop.,Verduzco-Castro EA, Michalska K, Endres M, Juarez-Vazquez AL, Noda-Garcia L, Chang C, Henry CS, Babnigg G, Joachimiak A, Barona-Gomez F Biochem J. 2016 May 1;473(9):1141-52. doi: 10.1042/BJ20151271. Epub 2016 Feb 29. PMID:26929404[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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