The Correct Phylogenetic Relationship of KdsA (3-Deoxy-D-manno-octulosonate 8-Phosphate Synthase) with One of Two Independently Evolved Classes of AroA (3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase)

Jensen, Roy A.; Xie, Gary; Calhoun, David H.; Bonner, Carol A.

doi:10.1007/s00239-001-0031-z

Cited by 56 publications

(71 citation statements)

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“…This unique feedback regulatory mechanism observed with the aroA and aroQ fusion proteins prompted us to re-examine the results from previous phylogenetic studies (8,9) that divided the microbial DAHPS family into two subfamilies. ClustalW (17) analysis of the amino acid sequence found that AroAI ␤ DAHPSs, to which aroA(Q) Bs and aroA(Q) Pg were assigned, appear to consist of two types of enzymes (Table 3), one with a shorter sequence defining a single DAHPS domain (type I, ϳ270 residues) and one with a longer sequence that contains a single DAHPS domain plus an extra segment with divergent sequences at either the N or C terminus (type II, ϳ350 residues).…”

Section: Discussionmentioning

confidence: 93%

“…It is interesting to note that this insertion, as well as either an N-or C-terminal fusion protein, is also missing in the structurally and functionally related catalytically unregulated KDOPS. Members of the KDOPS family, which are normally shorter in sequence (ϳ280 residues) than the regulated DAHPSs, have been assigned to the AroAI ␤ branch of the phylogenetic tree (9).…”

Section: Discussionmentioning

confidence: 99%

“…DAHPSs exist in both microorganisms and plants (2)(3)(4)(5)(6)(7)(8)(9). Utilizing a maximum likelihood-based grouping analysis, Birck and Woodard (8) divided 25 randomly chosen microbial DAHPS protein sequences into two classes (defined as Class I and Class II).…”

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confidence: 99%

“…KDOPS, a homologous enzyme involved in lipopolysaccharide biosynthesis, catalyzes a similar condensation reaction to that catalyzed by DAHPS, except between PEP and arabinose 5-phosphate (10). In a more inclusive-type analysis of over 100 DAHPS homologous amino acid sequences (including the KDOPSs) from both microbial and plant sources, performed by Jensen and colleagues (7,9,11), members of both enzymes were divided into two distinct main families (defined as AroAI and AroAII). The AroAII family, defined as "plant-like" DAHPS, are mainly plant proteins.…”

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confidence: 99%

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New Insights into the Evolutionary Links Relating to the 3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase Subfamilies

Woodard

2006

Journal of Biological Chemistry

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Bacterial 3-deoxy-d-arabino-heptulosonate 7-phosphate synthases (DAHPSs) have been divided into either of two classes (Class I/Class II) or subfamilies (AroAI ␣ /AroAI ␤ ). Our investigation into the biochemical properties of the unique bifunctional DAHPS from Bacillus subtilis provides new insight into the evolutionary link among DAHPS subfamilies. In the present study, the DAHPS (aroA) and chorismate mutase (aroQ) activities of B. subtilis DAHPS are separated by domain truncation. Detailed enzymatic studies with the full-length wild-type protein and the truncated domains led to our hypothesis that the aroQ domain was fused to the N terminus of aroA in B. subtilis during evolution for the purpose of feedback regulation and not for the creation of a bona fide bifunctional enzyme. In addition, examination of aroA and aroQ fusion proteins from Porphyromonas gingivalis, in which the aroQ domain is fused to the C terminus of aroA, further supports the hypothesis. These results, along with sequence structure analysis of the DAHPS families suggest that "feedback regulation" may indeed be the evolutionary link between the two classes/subfamilies. It is likely that DAHPSs evolved from a primitive unregulated member of the AroAI ␤ subfamily. During evolution, some members of the AroAI ␤ subfamily remained unregulated, whereas other members acquired an extra domain for feedback regulation. The AroAI ␣ subfamilies, however, evolved in a more complex manner to acquire insertions/ extensions in the (␤/␣) 8 barrel to function as regulatory elements.The first committed enzymatic step in the Shikimate biosynthetic pathway, the aldol-type condensation of phosphoenolpyruvate (PEP) 2 with erythrose 4-phosphate catalyzed by 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS; EC 4.1.2.15), is responsible for the biosynthesis of aromatic amino acids, folates, isoprenoid quinones, and other secondary metabolites in bacteria, fungi, and plants (1). DAHP, via six enzymatic steps, is converted into chorismate, the last common or branch point intermediate in the pathway. Chorismate is rearranged to prephenate by chorismate mutase (CM; EC 5.4.99.5) or to be converted into anthranilate by anthranilate synthase in the subsequent Phe/Tyr or Trp branch biosyntheses, respectively.DAHPSs exist in both microorganisms and plants (2-9). Utilizing a maximum likelihood-based grouping analysis, Birck and Woodard (8) divided 25 randomly chosen microbial DAHPS protein sequences into two classes (defined as Class I and Class II). In addition, 29 randomly chosen 3-deoxy-D-manno-octulosonate 8-phosphate synthases (KDOPS; EC 4.1.2.16) amino acid sequences were divided into two separate families of their own. KDOPS, a homologous enzyme involved in lipopolysaccharide biosynthesis, catalyzes a similar condensation reaction to that catalyzed by DAHPS, except between PEP and arabinose 5-phosphate (10). In a more inclusive-type analysis of over 100 DAHPS homologous amino acid sequences (including the KDOPSs) from both microbial and plant sources, perform...

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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New Insights into the Evolutionary Links Relating to the 3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase Subfamilies

Woodard

2006

Journal of Biological Chemistry

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“…This decoration of the barrel has been directly implicated in allosteric regulation of DAH7PS activity (8). DAH7PS enzymes have been divided into two types on the basis of protein size and amino acid sequence similarity (11): the smaller type I enzymes (30 -40 kDa), which can be further subdivided based on sequence into subtypes I␣ and I␤, and the larger type II enzymes (Ͼ50 kDa) (12,13). The sequence variability that defines the types and subtypes is directly paralleled in the structural variations that have been observed for DAH7PS enzymes (supplemental Fig.…”

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confidence: 99%

Tyrosine Latching of a Regulatory Gate Affords Allosteric Control of Aromatic Amino Acid Biosynthesis

Cross

Dobson

Patchett

et al. 2011

Journal of Biological Chemistry

104

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The first step of the shikimate pathway for aromatic amino acid biosynthesis is catalyzed by 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS). Thermotoga maritima DAH7PS (TmaDAH7PS) is tetrameric, with monomer units comprised of a core catalytic (␤/␣) 8 barrel and an N-terminal domain. This enzyme is inhibited strongly by tyrosine and to a lesser extent by the presence of phenylalanine. A truncated mutant of TmaDAH7PS lacking the N-terminal domain was catalytically more active and completely insensitive to tyrosine and phenylalanine, consistent with a role for this domain in allosteric inhibition. The structure of this protein was determined to 2.0 Å . In contrast to the wild-type enzyme, this enzyme is dimeric. Wild-type TmaDAH7PS was co-crystallized with tyrosine, and the structure of this complex was determined to a resolution of 2.35 Å . Tyrosine was found to bind at the interface between two regulatory N-terminal domains, formed from diagonally located monomers of the tetramer, revealing a major reorganization of the regulatory domain with respect to the barrel relative to unliganded enzyme. This significant conformational rearrangement observed in the crystal structures was also clearly evident from small angle X-ray scattering measurements recorded in the presence and absence of tyrosine. The closed conformation adopted by the protein on tyrosine binding impedes substrate entry into the neighboring barrel, revealing an unusual tyrosine-controlled gating mechanism for allosteric control of this enzyme.3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS, 2 E.C. 2.5.1.54) catalyzes the condensation reaction between phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) to form 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) (Fig. 1). This reaction is the first step in the shikimate pathway, which is used to synthesize chorismate, the precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, and of other important aromatic metabolites (1). The shikimate pathway is found in plants and microorganisms, and it has more recently been shown to function in apicomplexan parasites (49). As the shikimate pathway is absent in animals, the enzymes of this pathway have been identified as possible targets for the development of antimicrobial agents (2). Regulation of the catalytic activity of DAH7PS has been shown to be an important mechanism for control of cellular levels of aromatic compounds in microorganisms and plants (3).13 C NMR studies using whole cells of Escherichia coli have demonstrated that feedback inhibition of DAH7PS is the main mechanism for controlling carbon flow into the shikimate pathway (4). Different organisms employ various strategies for this feedback inhibition. E. coli, Salmonella typhimurium, and Neurospora crassa express three DAH7PS isozymes, each sensitive to a single aromatic amino acid (5, 6). In Saccharomyces cerevisiae, there are two DAH7PS isozymes; one is inhibited by phenylalanine, and the other is inhibited by tyrosine (7). Other org...

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The diversity of allosteric controls at the gateway to aromatic amino acid biosynthesis

Light

Anderson

2013

Protein Science

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Present within bacteria, plants, and some lower eukaryotes 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (DAHPS) catalyzes the first committed step in the synthesis of a number of metabolites, including the three aromatic amino acids phenylalanine, tyrosine, and tryptophan. Catalyzing the first reaction in an important biosynthetic pathway, DAHPS is situated at a critical regulatory checkpoint-at which pathway input can be efficiently modulated to respond to changes in the concentration of pathway outputs. Based on a phylogenetic classification scheme, DAHPSs have been divided into three major subtypes (Ia, Ib, and II). These subtypes are subjected to an unusually diverse pattern of allosteric regulation, which can be used to further subdivide the enzymes. Crystal structures of most of the regulatory subclasses have been determined. When viewed collectively, these structures illustrate how distinct mechanisms of allostery are applied to a common catalytic scaffold. Here, we review structural revelations regarding DAHPS regulation and make the case that the functional difference between the three major DAHPS subtypes relates to basic distinctions in quaternary structure and mechanism of allostery.

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The Correct Phylogenetic Relationship of KdsA (3-Deoxy-D-manno-octulosonate 8-Phosphate Synthase) with One of Two Independently Evolved Classes of AroA (3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase)

Cited by 56 publications

References 17 publications

New Insights into the Evolutionary Links Relating to the 3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase Subfamilies

New Insights into the Evolutionary Links Relating to the 3-Deoxy-D-arabino-heptulosonate 7-Phosphate Synthase Subfamilies

Tyrosine Latching of a Regulatory Gate Affords Allosteric Control of Aromatic Amino Acid Biosynthesis

The diversity of allosteric controls at the gateway to aromatic amino acid biosynthesis

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