Abstract
Homocysteine S-methyltransferases (HMTs) are widely distributed enzymes that convert homocysteine (Hcy) into methionine (Met) using either S-adenosylmethionine (AdoMet) or the plant secondary product S-methylmethionine (SMM) as methyl donor. AdoMet is chirally and covalently unstable, with racemization of natural (S,S)-AdoMet yielding biologically inactive (R,S)- AdoMet and depurination yielding S-ribosylmethionine (SribosylMet). The apparently futile AdoMet-dependent reaction of HMTs was assigned a role in repairing chiral damage to AdoMet in yeast: yeast HMTs strongly prefer (R,S)- to (S,S)-AdoMet and thereby limit (R,S)-AdoMet build-up [Vinci and Clarke (2010) J. Biol. Chem. 285, 20526-20531]. In the present study, we show that bacterial, plant, protistan and animal HMTs likewise prefer (R,S)- over (S,S)-AdoMet, that their ability to use SMM varies greatly and is associated with the likely prevalence of SMM in the environment of the organism and that most HMTs cannot use S-ribosylMet. Taken with results from comparative genomic and phylogenetic analyses, these data imply that (i) the ancestral function of HMTs was (R,S)-AdoMet repair, (ii) the efficient use of SMM reflects the repurposing of HMTs after the evolutionary advent of plants introduced SMM into the biosphere, (iii) this plant-driven repurposing was facile and occurred independently in various lineages, and (iv) HMTs have little importance in SribosylMet metabolism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 279-286 |
| Number of pages | 8 |
| Journal | Biochemical Journal |
| Volume | 463 |
| DOIs | |
| State | Published - Oct 15 2014 |
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Keywords
- Metabolite damage
- Methyl metabolism
- Neofunctionalization
- S-methylmethionine
- Vitamin U
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Medicine(all)
Cite this
Plant-driven repurposing of the ancient S-adenosylmethionine repair enzyme homocysteine S-methyltransferase. / Bradbury, Louis M T; Ziemak, Michael J.; El Badawi-Sidhu, Mona; Fiehn, Oliver; Hanson, Andrew D.
In: Biochemical Journal, Vol. 463, 15.10.2014, p. 279-286.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Plant-driven repurposing of the ancient S-adenosylmethionine repair enzyme homocysteine S-methyltransferase
AU - Bradbury, Louis M T
AU - Ziemak, Michael J.
AU - El Badawi-Sidhu, Mona
AU - Fiehn, Oliver
AU - Hanson, Andrew D.
PY - 2014/10/15
Y1 - 2014/10/15
N2 - Homocysteine S-methyltransferases (HMTs) are widely distributed enzymes that convert homocysteine (Hcy) into methionine (Met) using either S-adenosylmethionine (AdoMet) or the plant secondary product S-methylmethionine (SMM) as methyl donor. AdoMet is chirally and covalently unstable, with racemization of natural (S,S)-AdoMet yielding biologically inactive (R,S)- AdoMet and depurination yielding S-ribosylmethionine (SribosylMet). The apparently futile AdoMet-dependent reaction of HMTs was assigned a role in repairing chiral damage to AdoMet in yeast: yeast HMTs strongly prefer (R,S)- to (S,S)-AdoMet and thereby limit (R,S)-AdoMet build-up [Vinci and Clarke (2010) J. Biol. Chem. 285, 20526-20531]. In the present study, we show that bacterial, plant, protistan and animal HMTs likewise prefer (R,S)- over (S,S)-AdoMet, that their ability to use SMM varies greatly and is associated with the likely prevalence of SMM in the environment of the organism and that most HMTs cannot use S-ribosylMet. Taken with results from comparative genomic and phylogenetic analyses, these data imply that (i) the ancestral function of HMTs was (R,S)-AdoMet repair, (ii) the efficient use of SMM reflects the repurposing of HMTs after the evolutionary advent of plants introduced SMM into the biosphere, (iii) this plant-driven repurposing was facile and occurred independently in various lineages, and (iv) HMTs have little importance in SribosylMet metabolism.
AB - Homocysteine S-methyltransferases (HMTs) are widely distributed enzymes that convert homocysteine (Hcy) into methionine (Met) using either S-adenosylmethionine (AdoMet) or the plant secondary product S-methylmethionine (SMM) as methyl donor. AdoMet is chirally and covalently unstable, with racemization of natural (S,S)-AdoMet yielding biologically inactive (R,S)- AdoMet and depurination yielding S-ribosylmethionine (SribosylMet). The apparently futile AdoMet-dependent reaction of HMTs was assigned a role in repairing chiral damage to AdoMet in yeast: yeast HMTs strongly prefer (R,S)- to (S,S)-AdoMet and thereby limit (R,S)-AdoMet build-up [Vinci and Clarke (2010) J. Biol. Chem. 285, 20526-20531]. In the present study, we show that bacterial, plant, protistan and animal HMTs likewise prefer (R,S)- over (S,S)-AdoMet, that their ability to use SMM varies greatly and is associated with the likely prevalence of SMM in the environment of the organism and that most HMTs cannot use S-ribosylMet. Taken with results from comparative genomic and phylogenetic analyses, these data imply that (i) the ancestral function of HMTs was (R,S)-AdoMet repair, (ii) the efficient use of SMM reflects the repurposing of HMTs after the evolutionary advent of plants introduced SMM into the biosphere, (iii) this plant-driven repurposing was facile and occurred independently in various lineages, and (iv) HMTs have little importance in SribosylMet metabolism.
KW - Metabolite damage
KW - Methyl metabolism
KW - Neofunctionalization
KW - S-methylmethionine
KW - Vitamin U
UR - http://www.scopus.com/inward/record.url?scp=84907226785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907226785&partnerID=8YFLogxK
U2 - 10.1042/BJ20140753
DO - 10.1042/BJ20140753
M3 - Article
C2 - 25046177
AN - SCOPUS:84907226785
VL - 463
SP - 279
EP - 286
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
ER -