Structural basis for methylphosphonate biosynthesis

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Science  08 Dec 2017:
Vol. 358, Issue 6368, pp. 1336-1339
DOI: 10.1126/science.aao3435
  • Fig. 1 The reactions of MPnS and HEPD have been proposed to proceed through a common radical intermediate.

    The hydrogen derived from the C2 pro-R position in 2-HEP is highlighted in red throughout. The radical recombination in MPnS or HEPD (17) is colored red or blue, respectively. For an alternative mechanism involving a cationic intermediate, see fig. S9.

  • Fig. 2 Active-site structure of NmMPnS and SaHEPD.

    (A) The NmMPnS active site is composed of residues from the β1 domain (cyan) and the α1′ domain (pink), with two key residues discussed in the text in light brown. Fe(II) (orange sphere) is ligated by substrate, Gln152, His148, and His190. Although electron density cannot be used to distinguish oxygen from nitrogen, we are showing the oxygen of the Gln side chain coordinating Fe(II). (B) SaHEPD active site composed of residues from the β1 domain (yellow) and the α1′ domain (green) for two protomers of the asymmetric unit in which Gln153 is in the iron-binding conformation. (C) Alternative conformation of SaHEPD, where Gln153 is displaced from the Fe(II). Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.

  • Fig. 3 Proposed intermediates for MPnS and SaHEPD.

    (A) Gln152 in MPnS coordinates the formate intermediate, enabling H-atom abstraction by the MPn radical. (B) Formate displaces Gln153 from its iron-coordinating position in SaHEPD, preventing H-atom abstraction by the MPn-based radical and promoting reaction with the iron-bound hydroxide.

  • Fig. 4 Phylogeny of MPnS, HEPD, and HppE-like proteins.

    HEPD proteins are colored based on the iron-ligating facial triad: class I HEPD, 2-His-1-Glu (green); or class II HEPD, 2-His-1-Gln (brown). MPnS proteins are colored based on the amino acid at position 184, either Ile (blue) or Val (magenta). Complete labeling of sequence names is provided in fig. S10.

Supplementary Materials

  • Structural basis for methylphosphonate biosynthesis

    David A. Born, Emily C. Ulrich, Kou-San Ju, Spencer C. Peck, Wilfred A. van der Donk, Catherine L. Drennan

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Materials and Methods
    • Figs. S1 to S10
    • Tables S1 and S2
    • References
    Table S3
    MPnS, HEPD, and HppE-like sequences used in phylogenetic analysis.
    Table S4
    HEPD and MPnS sequences with iron-coordinating and specificity-determining residues indicated. The enzyme class for each sequence is annotated.

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