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Barrels in pieces?

Imidazole glycerol phosphate synthase (HisF) has been proposed to be the product of duplication of a gene encoding a (β/α)4-half barrel followed by fusion to encode the complete (β/α)8-barrel. In support of this evolutionary scenario, the N- and C-terminal (β/α)4-half barrels of HisF* have been separately expressed and purified. Each assumes a stable, soluble homodimeric structure, but neither is catalytically active; when expressed together, a functional heterodimer is formed.

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Figure 1: Reactions catalyzed by N-[(5′-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide isomerase (HisA) and imidazole glycerol phosphate synthase (HisF).
Figure 2: Superposition of HisF-N and HisF-C.
Figure 3: Hypothetical structures for HisF-NC (HisF-N)2, and (HisF-C)2 in which the HisF-N and HisF-C (β/α)4-half barrels are assembled to form parallel β-sheet structures; each is viewed from the C-terminal ends of the β-sheets.

Notes

  1. NOTE: A typographical error has been corrected in the web version of the News & Views article by John A. Gerlt and Patricia C. Babbitt. The sentence in the first paragraph, "In support of this evolutionary scenario...4-half barrels of TrpF have been separately expressed and purified" has had TrpF changed to HisF. We apologize for any confusion these errors may have caused. The most current version of the article is available in the PDF format.

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Correspondence to John A. Gerlt or Patricia C. Babbitt.

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Gerlt, J., Babbitt, P. Barrels in pieces?. Nat Struct Mol Biol 8, 5–7 (2001). https://doi.org/10.1038/83048

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