Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpol in yeast

Keisuke Mon, Takashi Obara, Naoya Seki, Masatoshi Miyamoto, Tatsuro Naganuma, Takuya Kitamura, Akio Kihara

研究成果: Article査読

抄録

The yeast protein Mpol belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpol is an Fe2+-dependent dioxygenase that catalyzes the α-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpol, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo 1 contains two transmembrane domains and that both its N- and C-terminal regions are exposed to the cytosol. Mutational analyses revealed that three histidine residues conserved in the Mpol family are especially important for Mpol activity, suggesting that they may be responsible for the formation of coordinate bonds with Fe2+. We found that, in addition to activity toward 2-OH long-chain FAs, Mpol also exhibits activity toward 2-OH very-long-chain FAs derived from the FA moiety of sphingoids. These results indicate that Mpo 1 is involved in the metabolism of long-chain to very-long-chain 2-OH FAs produced in different pathways. We noted that the growth of mpol A cells is delayed upon carbon deprivation, suggesting that the Mpol-mediated conversion of 2-OH FAs to non-hydroxy FAs is important for utilizing 2-OH FAs as a carbon source under carbon starvation. Our findings help to elucidate the as-yet-unknown functions and activities of other Mpol family members.

本文言語English
ジャーナルJournal of lipid research
61
7
DOI
出版ステータスPublished - 2020 7
外部発表はい

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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