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NTR: [polyprenol dehydrogenase activity] [dolichal reductase activity] [polyprenal reductase activity] #28566

Open sylvainpoux opened 1 month ago

sylvainpoux commented 1 month ago

Hi GO,

A recent paper published in Cell (PubMed=38821050) shows that the polyprenol reduction in dolichol biosynthesis is performed by different enzymes and steps instead of one.

It was initially supposed that SRD5A3; Q9H8P0 mediates the reduction of polyprenol into dolichol in one step.

But the paper shows that it is mediated via 3 steps: There is first a dehydrogenation of polyprenol into polyprenal (step1, mediated by DHRSX); polyprenal is then reduced into dolichal by SRD5A3 (step2), and dolichal is finally reduced into dolichol by DHRSX (step3).

I would need 3 new GO terms

Thanks

Sylvain

1) Term: polyprenol dehydrogenase activity Definition: Catalysis of the reaction: ditrans,polycis-polyprenol + NAD(P) = ditrans,polycis-polyprenal+ NAD(P)H + H+ child of: GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor There are 2 Rhea reaction, one for NAD and one for NADP [Rhea:80719] [Rhea:80723] PMID:38821050

2) Term: dolichal reductase activity Definition: Catalysis of the reaction: ditrans,polycis-dolichal+ H+ + NAD(P)H = a ditrans,polycis-dolichol+ NAD(P) child of: GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor PMID:38821050 There are 2 Rhea reaction, one for NAD and one for NADP [Rhea:80731] [Rhea:80735]

3) Term: polyprenal reductase activity Definition: Catalysis of the reaction: ditrans,polycis-polyprenal+ H+ + NADPH = ditrans,polycis-dolichal+ NADP child of: GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor PMID:38821050 [Rhea:80727] EC=1.3.1.94

4) polyprenol reductase activity [GO:0102389] should be deleted (please note that the former EC number 1.3.1.94 will be associated with the Polyprenal reductase activity (see term request 3)

raymond91125 commented 1 month ago

image

raymond91125 commented 1 month ago

The RHEA's are not public. Is there a way that we can see them? polyprenol reductase activity [GO:0102389] is also used to annotate PF3D7_1455900 (based on PMID:32764679). Has it been decided that EC:1.3.1.94 is to be renamed by IUBMB?

sylvainpoux commented 1 month ago

Hi @raymond91125

Here are the not-yet public Rhea reactions:

CC CATALYTIC ACTIVITY Reaction=a di-trans,poly-cis-dolichal + NADP(+) = a di-trans,poly-cis-polyprenal + H(+) + NADPH [Rhea:80727] EC=1.3.1.94 CC CATALYTIC ACTIVITY Reaction=a di-trans,poly-cis-polyprenol + NAD(+) = a di-trans,poly-cis-polyprenal + H(+) + NADH [Rhea:80719] CC CATALYTIC ACTIVITY Reaction=a di-trans,poly-cis-polyprenol + NADP(+) = a di-trans,poly-cis-polyprenal + H(+) + NADPH [Rhea:80723] CC CATALYTIC ACTIVITY Reaction=a di-trans,poly-cis-dolichol + NADP(+) = a di-trans,poly-cis-dolichal + H(+) + NADPH [Rhea:80731] CC CATALYTIC ACTIVITY Reaction=a di-trans,poly-cis-dolichol + NAD(+) = a di-trans,poly-cis-dolichal + H(+) + NADH [Rhea:80735]

I discussed with @kaxelsen who decided to change the reaction associated with 1.3.1.94 to match with the new reaction. As the EC number was associated with SRD5A3, we could not obsolete the EC number.

I cannot find any annotation related to PMID:32764679/PF3D7_1455900, but the paper is clearly not providing strong evidence for the polyprenol reductase activity.

Thanks

Sylvain

ValWood commented 1 month ago

Note to self, look for DHRSX ortholog

raymond91125 commented 1 month ago

I think it's fair to say that PMID:32764679 did not distinguish between the one-step reaction from multi-step polyprenol → dolichol.

I'm holding off changes to GO:0102389/EC:1.3.1.94 waiting for the official update at Expasy.

raymond91125 commented 1 month ago

+[Term] +id: GO:0160196 +name: polyprenol dehydrogenase activity +namespace: molecular_function +def: "Catalysis of the reaction: ditrans,polycis-polyprenol + NAD(P) = ditrans,polycis-polyprenal+ NAD(P)H + H+." [PMID:38821050] +xref: RHEA:80719 {source="skos:narrowMatch"} +xref: RHEA:80723 {source="skos:narrowMatch"} +is_a: GO:0016628 ! oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/28566" xsd:anyURI +created_by: rynl +creation_date: 2024-07-25T00:44:15Z + +[Term] +id: GO:0160197 +name: dolichal reductase activity +namespace: molecular_function +def: "Catalysis of the reaction: ditrans,polycis-dolichal+ H+ + NAD(P)H = ditrans,polycis-dolichol+ NAD(P)." [PMID:38821050] +xref: RHEA:80731 {source="skos:narrowMatch"} +xref: RHEA:80735 {source="skos:narrowMatch"} +is_a: GO:0016628 ! oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/28566" xsd:anyURI +created_by: rynl +creation_date: 2024-07-25T05:48:36Z + +[Term] +id: GO:0160198 +name: polyprenal reductase activity +namespace: molecular_function +def: "Catalysis of the reaction: ditrans,polycis-polyprenal+ H+ + NADPH = ditrans,polycis-dolichal+ NADP." [PMID:38821050] +xref: RHEA:80727 +is_a: GO:0016628 ! oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor +property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/28566" xsd:anyURI +created_by: rynl +creation_date: 2024-07-25T05:51:59Z