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PDBsum entry 4x9s
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References listed in PDB file
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Key reference
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Title
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Co-Occurrence of analogous enzymes determines evolution of a novel (βα)8-Isomerase sub-Family after non-Conserved mutations in flexible loop.
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Authors
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E.A.Verduzco-Castro,
K.Michalska,
M.Endres,
A.L.Juárez-Vazquez,
L.Noda-García,
C.Chang,
C.S.Henry,
G.Babnigg,
A.Joachimiak,
F.Barona-Gómez.
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Ref.
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Biochem J, 2016,
473,
1141-1152.
[DOI no: ]
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PubMed id
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Abstract
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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.
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