Limits...
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.

Show MeSH

Related in: MedlinePlus

Composite of alternative biochemical routes from chorismate (CHA) to L-tyrosine (TYR) in nature. An antibiotic synthesis branch from CHA is also shown (dimmed). Here the intermediates shown to intervene between chorismate and pristinamycin or chloramphenicol are p-aminochorismate (ADC), p-aminoprephenate (ADP), p-aminophenylpyruvate (APP), and p-aminophenylalanine (APA). PPA may be transaminated by prephenate aminotransferase (PAT) to yield L-arogenate (AGN). The four TyrA homologs and the reactions they catalyze are colored differently. Arogenate dehydrogenase (TyrAa) converts AGN to TYR. Alternatively, prephenate dehydrogenase (TyrAp) converts PPA to 4-hydroxyphenylpyruvate (HPP) which is then transaminated to TYR via an homolog of TyrB, AspC, HisH, or Tat [49]. A broad-specificity cyclohexadienyl dehydrogenase (TyrAc) is competent to catalyze either the TyrAa or the TyrAp reaction. PapC converts the 4-amino analog of PPA to the 4-amino analog of HPP. AroQ, AroH, and AroR are distinct homologs known to exist in nature for performance of the chorismate mutase reaction. Other abbreviations: AA, amino acid donor, KA, keto-acid accepter.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1173090&req=5

Figure 1: Composite of alternative biochemical routes from chorismate (CHA) to L-tyrosine (TYR) in nature. An antibiotic synthesis branch from CHA is also shown (dimmed). Here the intermediates shown to intervene between chorismate and pristinamycin or chloramphenicol are p-aminochorismate (ADC), p-aminoprephenate (ADP), p-aminophenylpyruvate (APP), and p-aminophenylalanine (APA). PPA may be transaminated by prephenate aminotransferase (PAT) to yield L-arogenate (AGN). The four TyrA homologs and the reactions they catalyze are colored differently. Arogenate dehydrogenase (TyrAa) converts AGN to TYR. Alternatively, prephenate dehydrogenase (TyrAp) converts PPA to 4-hydroxyphenylpyruvate (HPP) which is then transaminated to TYR via an homolog of TyrB, AspC, HisH, or Tat [49]. A broad-specificity cyclohexadienyl dehydrogenase (TyrAc) is competent to catalyze either the TyrAa or the TyrAp reaction. PapC converts the 4-amino analog of PPA to the 4-amino analog of HPP. AroQ, AroH, and AroR are distinct homologs known to exist in nature for performance of the chorismate mutase reaction. Other abbreviations: AA, amino acid donor, KA, keto-acid accepter.

Mentions: Dehydrogenases dedicated to L-tyrosine (TYR) biosynthesis comprise a family of TyrA homologs that have different specificities for the cyclohexadienyl substrate: ones specific for L-arogenate (AGN), ones specific for prephenate (PPA), and those that are able to use both [1,2]. Figure 1 illustrates the biochemical relationship of these specificities to divergent transformations beginning with chorismate (CHA) utilization and converging on TYR formation. Compounding this complexity, a given TyrA enzyme having any of the aforementioned cyclohexadienyl specificities may be specific for NAD+ or NADP+, or may use both. This is consistent with a growing appreciation [3,4] that different substrate specificities are often accommodated across a given protein family that nevertheless maintains a common scaffold of fundamental reaction chemistry. Even within the single category of broad TyrA specificity, there is a continuum ranging from examples where alternative substrates are accepted equally well to other cases where one substrate may be preferred by an order of magnitude or more. Table 1 provides a key to the nomenclature used to identify the various possible substrate-utilization combinations (both cyclohexadienyl and pyridine nucleotide) exhibited by TyrA proteins.


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

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

Composite of alternative biochemical routes from chorismate (CHA) to L-tyrosine (TYR) in nature. An antibiotic synthesis branch from CHA is also shown (dimmed). Here the intermediates shown to intervene between chorismate and pristinamycin or chloramphenicol are p-aminochorismate (ADC), p-aminoprephenate (ADP), p-aminophenylpyruvate (APP), and p-aminophenylalanine (APA). PPA may be transaminated by prephenate aminotransferase (PAT) to yield L-arogenate (AGN). The four TyrA homologs and the reactions they catalyze are colored differently. Arogenate dehydrogenase (TyrAa) converts AGN to TYR. Alternatively, prephenate dehydrogenase (TyrAp) converts PPA to 4-hydroxyphenylpyruvate (HPP) which is then transaminated to TYR via an homolog of TyrB, AspC, HisH, or Tat [49]. A broad-specificity cyclohexadienyl dehydrogenase (TyrAc) is competent to catalyze either the TyrAa or the TyrAp reaction. PapC converts the 4-amino analog of PPA to the 4-amino analog of HPP. AroQ, AroH, and AroR are distinct homologs known to exist in nature for performance of the chorismate mutase reaction. Other abbreviations: AA, amino acid donor, KA, keto-acid accepter.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Composite of alternative biochemical routes from chorismate (CHA) to L-tyrosine (TYR) in nature. An antibiotic synthesis branch from CHA is also shown (dimmed). Here the intermediates shown to intervene between chorismate and pristinamycin or chloramphenicol are p-aminochorismate (ADC), p-aminoprephenate (ADP), p-aminophenylpyruvate (APP), and p-aminophenylalanine (APA). PPA may be transaminated by prephenate aminotransferase (PAT) to yield L-arogenate (AGN). The four TyrA homologs and the reactions they catalyze are colored differently. Arogenate dehydrogenase (TyrAa) converts AGN to TYR. Alternatively, prephenate dehydrogenase (TyrAp) converts PPA to 4-hydroxyphenylpyruvate (HPP) which is then transaminated to TYR via an homolog of TyrB, AspC, HisH, or Tat [49]. A broad-specificity cyclohexadienyl dehydrogenase (TyrAc) is competent to catalyze either the TyrAa or the TyrAp reaction. PapC converts the 4-amino analog of PPA to the 4-amino analog of HPP. AroQ, AroH, and AroR are distinct homologs known to exist in nature for performance of the chorismate mutase reaction. Other abbreviations: AA, amino acid donor, KA, keto-acid accepter.
Mentions: Dehydrogenases dedicated to L-tyrosine (TYR) biosynthesis comprise a family of TyrA homologs that have different specificities for the cyclohexadienyl substrate: ones specific for L-arogenate (AGN), ones specific for prephenate (PPA), and those that are able to use both [1,2]. Figure 1 illustrates the biochemical relationship of these specificities to divergent transformations beginning with chorismate (CHA) utilization and converging on TYR formation. Compounding this complexity, a given TyrA enzyme having any of the aforementioned cyclohexadienyl specificities may be specific for NAD+ or NADP+, or may use both. This is consistent with a growing appreciation [3,4] that different substrate specificities are often accommodated across a given protein family that nevertheless maintains a common scaffold of fundamental reaction chemistry. Even within the single category of broad TyrA specificity, there is a continuum ranging from examples where alternative substrates are accepted equally well to other cases where one substrate may be preferred by an order of magnitude or more. Table 1 provides a key to the nomenclature used to identify the various possible substrate-utilization combinations (both cyclohexadienyl and pyridine nucleotide) exhibited by TyrA proteins.

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