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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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Alignment of the N-terminal glycine-rich P-loop of TyrA•ACT proteins from the Class Actinobacteria. These are specific for L-arogenate as substrate, but fall into two groups with respect to the pyridine nucleotide co-substrate. The top NAD+-specific group possesses an aspartate (D) at position 32 (E. coli numbering), whereas the bottom NAD+/NADP+ group possesses an asparagine at the homologous position. Residue numbers are shown at the left. The species in the middle are color coded to match the hierarchical taxon positions obtained from NCBI. The variable loop of the Wierenga fingerprint [26], which in E. coli contains five residues (22–26), contains the minimal two residues in all of the Actinobacteria shown. The organisms on the right are color coded according to the taxonomic position indicated on the left (NCBI). The Rubrobacter xylanophilus TyrAa sequence is an orphan in the tree displayed in Fig. 2, as consistent with its outlying position in the taxonomy scheme.
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Figure 4: Alignment of the N-terminal glycine-rich P-loop of TyrA•ACT proteins from the Class Actinobacteria. These are specific for L-arogenate as substrate, but fall into two groups with respect to the pyridine nucleotide co-substrate. The top NAD+-specific group possesses an aspartate (D) at position 32 (E. coli numbering), whereas the bottom NAD+/NADP+ group possesses an asparagine at the homologous position. Residue numbers are shown at the left. The species in the middle are color coded to match the hierarchical taxon positions obtained from NCBI. The variable loop of the Wierenga fingerprint [26], which in E. coli contains five residues (22–26), contains the minimal two residues in all of the Actinobacteria shown. The organisms on the right are color coded according to the taxonomic position indicated on the left (NCBI). The Rubrobacter xylanophilus TyrAa sequence is an orphan in the tree displayed in Fig. 2, as consistent with its outlying position in the taxonomy scheme.

Mentions: The TyrA sequences of Actinobacteria separate into two distinct groupings on the protein tree (Fig. 2). Coryneform bacteria in one sub-cluster have been rigorously characterized as the NAD(P)TyrAa substrate specificity type. On the other hand, a variety of Streptomyces species have been shown [23,24] to possess NADTyrAa, and TyrA proteins of these organisms populate the second Actinobacteria sub-cluster of Fig. 2. Figure 4 shows sequence alignments of the N-terminal pyridine-nucleotide discriminator regions of currently available actinomycetes. The conserved 'D' residue (highlighted in yellow) in the upper group is a reliable indicator of NAD+ specificity, in part because NADP+ is repelled by the negative charge at this position. The asparagine residue (highlighted in blue) in the corresponding position in members of the lower group indicates NAD(P)+ specificity as discussed by Bonner et al. [25]. Rubrobacter xylanophilus is the most distant representative of the Actinobacteria, being the sole member of the subclass taxon Rubrobacteridae, and its protein (denoted Rxyl) appears as an orphan in Fig. 2.


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

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

Alignment of the N-terminal glycine-rich P-loop of TyrA•ACT proteins from the Class Actinobacteria. These are specific for L-arogenate as substrate, but fall into two groups with respect to the pyridine nucleotide co-substrate. The top NAD+-specific group possesses an aspartate (D) at position 32 (E. coli numbering), whereas the bottom NAD+/NADP+ group possesses an asparagine at the homologous position. Residue numbers are shown at the left. The species in the middle are color coded to match the hierarchical taxon positions obtained from NCBI. The variable loop of the Wierenga fingerprint [26], which in E. coli contains five residues (22–26), contains the minimal two residues in all of the Actinobacteria shown. The organisms on the right are color coded according to the taxonomic position indicated on the left (NCBI). The Rubrobacter xylanophilus TyrAa sequence is an orphan in the tree displayed in Fig. 2, as consistent with its outlying position in the taxonomy scheme.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1173090&req=5

Figure 4: Alignment of the N-terminal glycine-rich P-loop of TyrA•ACT proteins from the Class Actinobacteria. These are specific for L-arogenate as substrate, but fall into two groups with respect to the pyridine nucleotide co-substrate. The top NAD+-specific group possesses an aspartate (D) at position 32 (E. coli numbering), whereas the bottom NAD+/NADP+ group possesses an asparagine at the homologous position. Residue numbers are shown at the left. The species in the middle are color coded to match the hierarchical taxon positions obtained from NCBI. The variable loop of the Wierenga fingerprint [26], which in E. coli contains five residues (22–26), contains the minimal two residues in all of the Actinobacteria shown. The organisms on the right are color coded according to the taxonomic position indicated on the left (NCBI). The Rubrobacter xylanophilus TyrAa sequence is an orphan in the tree displayed in Fig. 2, as consistent with its outlying position in the taxonomy scheme.
Mentions: The TyrA sequences of Actinobacteria separate into two distinct groupings on the protein tree (Fig. 2). Coryneform bacteria in one sub-cluster have been rigorously characterized as the NAD(P)TyrAa substrate specificity type. On the other hand, a variety of Streptomyces species have been shown [23,24] to possess NADTyrAa, and TyrA proteins of these organisms populate the second Actinobacteria sub-cluster of Fig. 2. Figure 4 shows sequence alignments of the N-terminal pyridine-nucleotide discriminator regions of currently available actinomycetes. The conserved 'D' residue (highlighted in yellow) in the upper group is a reliable indicator of NAD+ specificity, in part because NADP+ is repelled by the negative charge at this position. The asparagine residue (highlighted in blue) in the corresponding position in members of the lower group indicates NAD(P)+ specificity as discussed by Bonner et al. [25]. Rubrobacter xylanophilus is the most distant representative of the Actinobacteria, being the sole member of the subclass taxon Rubrobacteridae, and its protein (denoted Rxyl) appears as an orphan in Fig. 2.

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