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The TyrA family of aromatic-pathway dehydrogenases in phylogenetic context.

Song J, Bonner CA, Wolinsky M, Jensen RA - BMC Biol. (2005)

Bottom Line: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates.The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria.The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

View Article: PubMed Central - HTML - PubMed

Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. jian@lanl.gov

ABSTRACT

Background: The TyrA protein family includes members that catalyze two dehydrogenase reactions in distinct pathways leading to L-tyrosine and a third reaction that is not part of tyrosine biosynthesis. Family members share a catalytic core region of about 30 kDa, where inhibitors operate competitively by acting as substrate mimics. This protein family typifies many that are challenging for bioinformatic analysis because of relatively modest sequence conservation and small size.

Results: Phylogenetic relationships of TyrA domains were evaluated in the context of combinatorial patterns of specificity for the two substrates, as well as the presence or absence of a variety of fusions. An interactive tool is provided for prediction of substrate specificity. Interactive alignments for a suite of catalytic-core TyrA domains of differing specificity are also provided to facilitate phylogenetic analysis. tyrA membership in apparent operons (or supraoperons) was examined, and patterns of conserved synteny in relationship to organismal positions on the 16S rRNA tree were ascertained for members of the domain Bacteria. A number of aromatic-pathway genes (hisHb, aroF, aroQ) have fused with tyrA, and it must be more than coincidental that the free-standing counterparts of all of the latter fused genes exhibit a distinct trace of syntenic association.

Conclusion: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates. Indeed, TyrA proteins of this type persist today, but it is also common to find instances of narrowed substrate specificities, as well as of acquisition via gene fusion of additional catalytic domains or regulatory domains. In some clades a qualitative change associated with either narrowed substrate specificity or gene fusion has produced an evolutionary "jump" in the vertical genealogy of TyrA homologs. The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria. The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

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Multiple alignment of the HMM consensus sequences obtained for different substrate-specificity groupings within cyclohexadienyl-substrate core segments (see Table 3). Invariant anchor residues are highlighted in yellow, conserved residues in grey. These consensus sequences will change continuously as corrections and refinements are made. The version shown was current as of April, 2005.
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Figure 3: Multiple alignment of the HMM consensus sequences obtained for different substrate-specificity groupings within cyclohexadienyl-substrate core segments (see Table 3). Invariant anchor residues are highlighted in yellow, conserved residues in grey. These consensus sequences will change continuously as corrections and refinements are made. The version shown was current as of April, 2005.

Mentions: Our collection of curated TyrA sequences at AroPath (see Table 3) contains trimmed sequences that comprise catalytic-core domains. This collection was divided into two groups based on whether the sequences contained the relatively short N-terminal pyridine-nucleotide discriminator segment or the longer C-terminal cyclohexadienyl-substrate core segment. The sequences in the latter group were assembled into subgroups representing established substrate specificities (TyrAa, TyrAp and TyrAc) and were aligned separately to obtain overall consensus sequences for cyclohexadienyl-substrate core segments. The TyrAc group members from the lower-gamma assemblage of Proteobacteria (as well as from a few other lineages) were so distinctive that a fourth group (TyrAc_Δ) was defined. This latter group is, in fact, the most divergent of the four. Figure 3 shows a comparison of the four consensus sequences, with invariant anchor residues shaded yellow and residues conserved across all groups shaded in gray. Residues within each group that are >50% conserved are shown in capital letters. In pairwise BLAST (Basic Local Alignment Tool) [16]comparisons, TyrAa and TyrAc consensus sequences are most similar (47% identity), followed by the TyrAc/TyrAp pair (40% identity), with TyrAa and TyrAp exhibiting 34% identity. TyrAc_Δ is quite distinct from the other three groupings, exhibiting only 27% identity with TyrAc, 23% identity with TyrAc, and 18% identity with TyrAp.


The TyrA family of aromatic-pathway dehydrogenases in phylogenetic context.

Song J, Bonner CA, Wolinsky M, Jensen RA - BMC Biol. (2005)

Multiple alignment of the HMM consensus sequences obtained for different substrate-specificity groupings within cyclohexadienyl-substrate core segments (see Table 3). Invariant anchor residues are highlighted in yellow, conserved residues in grey. These consensus sequences will change continuously as corrections and refinements are made. The version shown was current as of April, 2005.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1173090&req=5

Figure 3: Multiple alignment of the HMM consensus sequences obtained for different substrate-specificity groupings within cyclohexadienyl-substrate core segments (see Table 3). Invariant anchor residues are highlighted in yellow, conserved residues in grey. These consensus sequences will change continuously as corrections and refinements are made. The version shown was current as of April, 2005.
Mentions: Our collection of curated TyrA sequences at AroPath (see Table 3) contains trimmed sequences that comprise catalytic-core domains. This collection was divided into two groups based on whether the sequences contained the relatively short N-terminal pyridine-nucleotide discriminator segment or the longer C-terminal cyclohexadienyl-substrate core segment. The sequences in the latter group were assembled into subgroups representing established substrate specificities (TyrAa, TyrAp and TyrAc) and were aligned separately to obtain overall consensus sequences for cyclohexadienyl-substrate core segments. The TyrAc group members from the lower-gamma assemblage of Proteobacteria (as well as from a few other lineages) were so distinctive that a fourth group (TyrAc_Δ) was defined. This latter group is, in fact, the most divergent of the four. Figure 3 shows a comparison of the four consensus sequences, with invariant anchor residues shaded yellow and residues conserved across all groups shaded in gray. Residues within each group that are >50% conserved are shown in capital letters. In pairwise BLAST (Basic Local Alignment Tool) [16]comparisons, TyrAa and TyrAc consensus sequences are most similar (47% identity), followed by the TyrAc/TyrAp pair (40% identity), with TyrAa and TyrAp exhibiting 34% identity. TyrAc_Δ is quite distinct from the other three groupings, exhibiting only 27% identity with TyrAc, 23% identity with TyrAc, and 18% identity with TyrAp.

Bottom Line: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates.The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria.The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

View Article: PubMed Central - HTML - PubMed

Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. jian@lanl.gov

ABSTRACT

Background: The TyrA protein family includes members that catalyze two dehydrogenase reactions in distinct pathways leading to L-tyrosine and a third reaction that is not part of tyrosine biosynthesis. Family members share a catalytic core region of about 30 kDa, where inhibitors operate competitively by acting as substrate mimics. This protein family typifies many that are challenging for bioinformatic analysis because of relatively modest sequence conservation and small size.

Results: Phylogenetic relationships of TyrA domains were evaluated in the context of combinatorial patterns of specificity for the two substrates, as well as the presence or absence of a variety of fusions. An interactive tool is provided for prediction of substrate specificity. Interactive alignments for a suite of catalytic-core TyrA domains of differing specificity are also provided to facilitate phylogenetic analysis. tyrA membership in apparent operons (or supraoperons) was examined, and patterns of conserved synteny in relationship to organismal positions on the 16S rRNA tree were ascertained for members of the domain Bacteria. A number of aromatic-pathway genes (hisHb, aroF, aroQ) have fused with tyrA, and it must be more than coincidental that the free-standing counterparts of all of the latter fused genes exhibit a distinct trace of syntenic association.

Conclusion: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates. Indeed, TyrA proteins of this type persist today, but it is also common to find instances of narrowed substrate specificities, as well as of acquisition via gene fusion of additional catalytic domains or regulatory domains. In some clades a qualitative change associated with either narrowed substrate specificity or gene fusion has produced an evolutionary "jump" in the vertical genealogy of TyrA homologs. The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria. The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry.

Show MeSH
Related in: MedlinePlus