8000 lipoate synthase activity GO and Rhea definitions differ · Issue #30187 · geneontology/go-ontology · GitHub
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lipoate synthase activity GO and Rhea definitions differ #30187

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ValWood opened this issue Apr 27, 2025 · 2 comments
Open

lipoate synthase activity GO and Rhea definitions differ #30187

ValWood opened this issue Apr 27, 2025 · 2 comments

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@ValWood
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ValWood commented Apr 27, 2025 •
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GO
Catalysis of the reaction: protein N6-(octanoyl)lysine + 2 sulfur + 2 S-adenosyl-L-methionine = protein N6-(lipoyl)lysine + 2 L-methionine + 2 5'-deoxyadenosyl. [PMID:18307109]

Rhea
[[Fe-S] cluster scaffold protein carrying a second + N6-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 [S-adenosyl-L-methionine] + 4H = [[Fe-S] cluster scaffold protein] + N6-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 [Fe3+] + 2 [hydrogen sulfide] + 2 [5'-deoxyadenosine] + 2 [L-methionine] + reduced [2Fe-2S]-[ferredoxin]

see below
@cmungall
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I think something went wrong in your copy and paste from the RHEA website, the actual RHEA definition (https://www.rhea-db.org/rhea/16585) corresponds to the current EC definition according to Expasy:

[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) = [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin]

(it's interesting to see how RHEA represents scaffold proteins carrying a cluster, using a RHEA-COMP ID)

The GO definition corresponds closely to the 2012 version of EC: https://web.archive.org/web/20120916205731/https://enzyme.expasy.org/EC/2.8.1.8

(we probably took it from an earlier version and have never refreshed)

It's still very concerning to me why ExploreEnv (the official website of the IUBMB) doesn't sync with expasy:

https://www.enzyme-database.org/query.php?ec=2.8.1.8
[protein]-N6-(octanoyl)-L-lysine + an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]2+ cluster + 2 S-adenosyl-L-methionine + 2 oxidized [2Fe-2S] ferredoxin + 6 H+ = [protein]-N6-[(R)-dihydrolipoyl]-L-lysine + an [Fe-S] cluster scaffold protein + 2 sulfide + 4 Fe3+ + 2 L-methionine + 2 5′-deoxyadenosine + 2 reduced [2Fe-2S] ferredoxin

This is very close to what Expasy had in 2019: https://web.archive.org/web/20190322162618/https://enzyme.expasy.org/EC/2.8.1.8

Also the PMID on the radical SAM family doesn't seem the best source of a definition

@cmungall
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TL;DR:

  • use the RHEA definition [[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) = [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin]
  • use only the RHEA ID as def xref
  • keep xrefs as is

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