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Structure of Allium lachrymatory factor synthase elucidates catalysis on sulfenic acid substrate

View ORCID ProfileTakatoshi Arakawa, Yuta Sato, Jumpei Takabe, Noriya Masamura, Masahiro Kato, Morihiro Aoyagi, Takahiro Kamoi, Nobuaki Tsuge, Shinsuke Imai, View ORCID ProfileShinya Fushinobu
doi: https://doi.org/10.1101/142687
Takatoshi Arakawa
aGraduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
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  • ORCID record for Takatoshi Arakawa
  • For correspondence: arakawa@mail.ecc.u-tokyo.ac.jp
Yuta Sato
aGraduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
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Jumpei Takabe
aGraduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
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Noriya Masamura
bBasic Research Division, Central Research & Development Institute, House Foods Group Inc., Yotsukaido, 284-0033, Japan.
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Masahiro Kato
bBasic Research Division, Central Research & Development Institute, House Foods Group Inc., Yotsukaido, 284-0033, Japan.
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Morihiro Aoyagi
bBasic Research Division, Central Research & Development Institute, House Foods Group Inc., Yotsukaido, 284-0033, Japan.
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Takahiro Kamoi
bBasic Research Division, Central Research & Development Institute, House Foods Group Inc., Yotsukaido, 284-0033, Japan.
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Nobuaki Tsuge
bBasic Research Division, Central Research & Development Institute, House Foods Group Inc., Yotsukaido, 284-0033, Japan.
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Shinsuke Imai
bBasic Research Division, Central Research & Development Institute, House Foods Group Inc., Yotsukaido, 284-0033, Japan.
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Shinya Fushinobu
aGraduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
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  • ORCID record for Shinya Fushinobu
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Abstract

Natural lachrymatory effects are invoked by small volatile S-oxide compounds. They are produced through alkene sulfenic acids by the action of lachrymatory factor synthase (LFS). Here we present the crystal structures of onion LFS (AcLFS) revealed in solute-free and two solute-stabilized forms. Each structure adopts a single seven-stranded helix-grip fold possessing an internal pocket. Mutagenesis analysis localized the active site to a layer near the bottom of the pocket, which is adjacent to the deduced key residues Arg71, Glu88, and Tyr114. Solute molecules visible on the active site have suggested that AcLFS accepts various small alcohol compounds as well as its natural substrate, and they inhibit this substrate according to their chemistry. Structural homologs have been found in the SRPBCC superfamily, and comparison of the active sites has demonstrated that the electrostatic potential unique to AcLFS could work in capturing the substrate in its specific state. Finally, we propose a rational catalytic mechanism based on intramolecular proton shuttling in which the microenvironment of AcLFS can bypass the canonical [1,4]-sigmatropic rearrangement principle established by microwave studies. Beyond revealing how AcLFS generates the lachrymatory compound, this study provides insights into the molecular machinery dealing with highly labile organosulfur species.

Significance statement Crushing of onion liberates a volatile compound, syn-propanethial S-oxide (PTSO), which causes lachrymatory effect on humans. We present the crystal structures of onion LFS (AcLFS), the enzyme responsible for natural production of PTSO. AcLFS features a barrel-like fold, and mutagenic and inhibitory analyses revealed that the key residues are present in the central pocket, harboring highly concentrated aromatic residues plus a dyad motif. The architecture of AcLFS is widespread among proteins with various biological functions, such as abscisic acid receptors and polyketide cyclases, and comparisons with these homologs indicate that unique steric and electronic properties maintain the pocket as a reaction compartment. We propose the molecular mechanism behind PTSO generation and shed light on biological decomposition of short-lived sulfur species.

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Posted May 30, 2017.
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Structure of Allium lachrymatory factor synthase elucidates catalysis on sulfenic acid substrate
Takatoshi Arakawa, Yuta Sato, Jumpei Takabe, Noriya Masamura, Masahiro Kato, Morihiro Aoyagi, Takahiro Kamoi, Nobuaki Tsuge, Shinsuke Imai, Shinya Fushinobu
bioRxiv 142687; doi: https://doi.org/10.1101/142687
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Structure of Allium lachrymatory factor synthase elucidates catalysis on sulfenic acid substrate
Takatoshi Arakawa, Yuta Sato, Jumpei Takabe, Noriya Masamura, Masahiro Kato, Morihiro Aoyagi, Takahiro Kamoi, Nobuaki Tsuge, Shinsuke Imai, Shinya Fushinobu
bioRxiv 142687; doi: https://doi.org/10.1101/142687

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