Changes to children of GO:0016462 pyrophosphatase activity

[pgaudet]

In the ticket #23319 @sjm41 uncovered several modifications that should be made to children of GO:0016462 pyrophosphatase activity. Terms and suggested changes are here: https://docs.google.com/spreadsheets/d/1_LSxmArtht1kj4cuHjTBKUgokwgqHF1keM8KLugAQoY/edit#gid=0

• [ ] GO:0097382 deoxynucleoside-diphosphatase activity : grouping term for a single term, GO:0097383 dIDP diphosphatase activity. No annotations == > obsolete
• [x] move GO:0097383 dIDP diphosphatase activity under GO:0017110 nucleoside-diphosphatase activity [+]

• GO:0004551 nucleotide diphosphatase activity:

• [x] remove EC:3.6.1.9, which corresponds to GO:0047429 nucleoside-triphosphate diphosphatase activity (EC already correctly on GO:0047429)
• [x] change label to dinucleotide phosphatase activity

-- | --

[pgaudet]

• [x] GO:0017111 nucleoside-triphosphatase activity:

• change label to nucleoside triphosphate phosphatase activity
• Add back EC:3.6.1.15

[pgaudet]

• [x] GO:0017110 nucleoside-diphosphatase activity

• change label to nucleoside diphosphate phosphatase activity

[pgaudet]

GO:0052842 inositol diphosphate pentakisphosphate diphosphatase activity GO:0052840 inositol diphosphate tetrakisphosphate diphosphatase activity

==> remove EC:3.6.1.52; this is correctly on GO:0008486 diphosphoinositol-polyphosphate diphosphatase activity but not relevant for tetra and penta

[pgaudet]

DONE

'bis(5'-adenosyl)-hexaphosphatase activity' 'bis(5'-adenosyl)-pentaphosphatase activity' 'bis(5'-adenosyl)-triphosphatase activity' 'bis(5'-nucleosyl)-tetraphosphatase activity' are children of GO:0004551 'dinucleotide phosphatase activity' - this is incorrect as the substrates are not dinucleotides

===>> move terms directly under 'pyrophosphatase'

[pgaudet]

From @sjm41 References for GO:0004551

Nakajima Y, Fukunaga N, Sasaki S, Usami S (1973). "Purification and properties of NADP pyrophosphatase from Proteus vulgaris". Biochim. Biophys. Acta. 293 (1): 242–55. doi:10.1016/0005-2744(73)90397-5. PMID 4405504

Shin HJ, Mego JL (1988). "A rat liver lysosomal membrane flavin-adenine dinucleotide phosphohydrolase: purification and characterization". Arch. Biochem. Biophys. 267 (1): 95–103. doi:10.1016/0003-9861(88)90012-4. PMID 2848456

[pgaudet]

Dear all,

The proposal has been made to obsolete

• [x] GO:0097382 deoxynucleoside-diphosphatase activity : grouping term for a single term, GO:0097383 dIDP diphosphatase activity. No annotations, no mappings, not present in any subsets
• [ ] GO:0010943 NADPH pyrophosphatase activity: no reference, no annotations, no mapping. There is no evidence that this reaction exists.

You can comment on the ticket: https://github.com/geneontology/go-ontology/issues/23401

[pgaudet]

@sjm41 I think GO:0010943 NADPH pyrophosphatase activity corresponds to RHEA:60820

[pgaudet]

Standardized term labels:

• [x] GO:0004382 guanosine-diphosphatase activity -> GDP diphosphatase activity
• [x] GO:0036384 cytidine-diphosphatase activity -> CDP diphosphatase activity
• [x] GO:0043262 adenosine-diphosphatase activity -> ADP diphosphatase activity
• [x] GO:0045134 uridine-diphosphatase activity -> UDP diphosphatase activity
• [x] GO:1990003 inosine-diphosphatase activity -> IDP diphosphatase activity

[sjm41]

I think GO:0010943 NADPH pyrophosphatase activity corresponds to RHEA:60820

Ah yes, that's looks correct. And rhea says it's used on 1,396 UniProt proteins, so we should probably keep the GO term (even though no-one has used it to date!)

I see we can also add RHEA:48868 to NADH pyrophosphatase activity | GO:0035529

[paolaroncaglia]

@pgaudet @deustp01 Hi, FYI, GO:0097382 'deoxynucleoside-diphosphatase activity' was originally requested by Peter for Reactome. I don't oppose its obsoletion, but I'm pointing this out in case Peter wishes to comment. His original request is here. Thank you and best wishes! Paola

[sjm41]

Standardized term labels:

GO:0004382 guanosine-diphosphatase activity -> GDP diphosphatase activity GO:0036384 cytidine-diphosphatase activity -> CDP diphosphatase activity GO:0043262 adenosine-diphosphatase activity -> ADP diphosphatase activity GO:0045134 uridine-diphosphatase activity -> UDP diphosphatase activity GO:1990003 inosine-diphosphatase activity -> IDP diphosphatase activity

@pgaudet I think the new names here should be just 'XXX phosphatase activity' rather than 'XXX diphosphatase activity' E.g. GO:0004382 is "Catalysis of the reaction: GDP + H2O = GMP + phosphate"

[sjm41]

@paolaroncaglia @deustp01 The original term Peter requested (GO:0097383 dIDP diphosphatase activity) is being retained but under the grouping term "nucleoside diphosphate phosphatase activity (GO:0017110)". That grouping term already has several child terms, whereas the "deoxynucleoside-diphosphatase activity" grouping term only had that single child. The change is consistent with how GO already organises children of "nucleoside triphosphate diphosphatase activity (GO:0047429)".

[pgaudet]

thanks @sjm41 The children of 'nucleoside diphosphate phosphatase activity' are now:

'8-hydroxy-dADP phosphatase activity' '8-oxo-dADP phosphatase activity' '8-oxo-dGDP phosphatase activity' '8-oxo-GDP phosphatase activity' 'ADP phosphatase activity' 'CDP phosphatase activity' 'dIDP phosphatase activity' 'GDP phosphatase activity' 'IDP phosphatase activity' 'thiamine diphosphatase activity' 'UDP phosphatase activity'

[sjm41]

@pgaudet We changed the name of thymidine-triphosphatase activity (GO:0050339) to 'TTPase activity', but I think it should be 'dTTPase activity' to match the definition and xref. ('thymidine' is a synonym for 'deoxythymidine'/'dT')

[sjm41]

@pgaudet Sorry, some confusion over the 2 terms involving 'thiamine'. As wikipedia says, 'thiamine' (aka vitamin B1) should not be confused with 'Thymine' or 'Thymidine'....

So, these two terms should be moved to be direct children of 'pyrophosphatase activity':

• [x] thiamine-triphosphatase activity (GO:0050333)

Catalysis of the reaction: H(2)O + thiamine triphosphate = H(+) + phosphate + thiamine diphosphate (EC:3.6.1.28, RHEA:11744)

• [x] thiamine-diphosphatase activity (GO:0004787)

Catalysis of the reaction: TPP + H2O = TMP + phosphate. (RHEA:27998)

[deustp01]

So, these two terms should be moved to be direct children of 'pyrophosphatase activity':

Something is wrong here. GO:0016462 pyrophosphatase activity is "Catalysis of the hydrolysis of a pyrophosphate bond between two phosphate groups, leaving one phosphate on each of the two fragments" but RHEA:11744 shows a phosphatase reaction (removal of a single phosphate group as free phosphate, not attached to anything). Likewise for GO:0004787 - that looks like phosphatase activity, not pyrophosphatase activity.

[deustp01]

I'm pointing this out in case Peter wishes to comment.

And apologize - I can't remember why we made this request. We have the NUDT16 reaction with dIDP diphosphatase activity (GO:0097383) enabling it as Steve also noted, so I can no longer figure out why we asked for the additional term. If we wanted it for grouping, then the discussion above provides alternatives, and so no objection here to obsoletion.

[sjm41]

@deustp01 I think the GO def should probably omit the "leaving one phosphate on each of the two fragments" bit and just say "Catalysis of the hydrolysis of a pyrophosphate bond between two phosphate groups."

What do you think?

There's no reference for the current GO def and I can't easily find a good definition/reference from web searches. Certainly nothing saying a phosphate must remain attached to each fragment. Do you know of a good reference saying that?

Note that GO:0050333/RHEA:11744/3.6.1.28 and GO:0004787/RHEA:27998 are both already classified under pyrophosphase activity GO:0016462 (and thereby under EC:3.6.1.- via its parent GO term) in the current public GO. I don't think they should/can be classified under the regular 'phosphatase activity' GO:0016791 term as that term is defined as "Catalysis of the hydrolysis of phosphoric monoesters" and represents a different branch of EC (3.1.3.-).

[deustp01]

What do you think?

I think I'm out of my depth, arguing about the EC distinctions, which have both history and real expertise in chemistry behind them.

I was relying on my recollection of textbook biochemistry. Pyrophosphate (diphosphate; CHEBI:33019 - diphosphate(3−)) is released in many biosynthetic reactions. "The splitting of inorganic pyrophosphate (PPi) to two phosphate (Pi) groups is catalyzed by pyrophosphatases that apparently occur universally. Their function appears to be simply to remove the product PPi from reactions that produce it, shifting the equilibrium toward formation of a desired compound." (Metzler, "Biochemistry: The Chemical Reactions of Living Cells" 1st ed., 1977 - page 635). One could extrapolate from there to assert that hydrolysis between the two phosphate groups in a molecule R1-Pi-Pi- R2 to yield R1-Pi + R2-Pi is an example of pyrophosphatase activity (because the pyrophosphate moiety is what actually is cleaved) while hydrolysis of R-Pi-Pi-Pi to yield R-Pi-Pi + Pi is phosphatase activity.

That may be logical but, apparently, not standard reasoning.

[pgaudet]

@sjm41

With respect to your comment above, https://github.com/geneontology/go-ontology/issues/23401#issuecomment-1143737394

• [x] thiamine-triphosphatase activity (GO:0050333) -> I think this be moved under a more specific term, 'nucleoside triphosphate phosphatase activity', and be renamed 'thiamine triphosphate phosphatase activity'
• [x] thiamine-diphosphatase activity (GO:0004787) -> can be moved under 'nucleoside diphosphate phosphatase activity' (this was already done)

[pgaudet]

• [x] need to look at the definition of GO:0017111; in GO the substrate is a nucleoside triphosphate , in RHEA (RHEA:23680) it's a ribonucleoside triphosphate - not consistent

[pgaudet]

• [x] XTP diphosphatase activity, moved from -is_a: GO:0017111 ! nucleoside triphosphate phosphatase activity to +is_a: GO:0047429 ! nucleoside triphosphate diphosphatase activity

[deustp01]

• need to look at the definition of GO:0017111; in GO the substrate is a nucleoside triphosphate , in RHEA (RHEA:23680) it's a ribonucleoside triphosphate - not consistent

In ChEBI, CHEBI:61557 - nucleoside 5'-triphoshate(4−) is_a ribonucleoside 5'-triphosphate(4−), so it looks like there's a parentage issue at ChEBI (also a spelling issue - missing p in phoshate).

Meanwhile, there is a RHEA reaction for dNTP's, RHEA:64916 with 2'-deoxyribonucleoside 5'-triphosphate(4−) (CHEBI:61560) as input.

[pgaudet]

As far as @sjm41 and I can tell, Thiamine is a pyrimidine but not a nucleoside - ie it doesn't have a sugar attached. So we'll move it from is_a 'nucleoside triphosphate phosphatase activity' to is_a 'pyrophosphatase'

@kaxelsen if you have a minute to check this, we'd much appreciate it.

[pgaudet]

• [x] thiamine phosphate phosphatase activity addxrefs:

• RHEA:47948 | H2O + thiamine phosphate = phosphate + thiamine |
• EC:3.1.3.100 Thiamine phosphate phosphatase

[pgaudet]

Fixed definition of pyrophophatase activity from: Catalysis of the hydrolysis of a pyrophosphate bond between two phosphate groups, leaving one phosphate on each of the two fragments. to: 'Catalysis of the hydrolysis of a pyrophosphate bond (diphosphate bond) between two phosphate groups.'

The old definition was a bit confusing, since sometimes only phosphate or the diphosphate is left after hydrolysis (and not a phosphate + some other group).

[sjm41]

• [x] add EC:3.6.1.67 as xref to GO:0019177 dihydroneopterin triphosphate pyrophosphohydrolase activity

[kaxelsen]

There are many things to be corrected in this thread. First of all there is the definition of GO:0016462 I see in this comment: "Catalysis of the hydrolysis of a pyrophosphate bond between two phosphate groups, leaving one phosphate on each of the two fragments".

For this to be able to be fulfilled, it requires the diphosphate moiety is situated in the middle of the substrate as for example in NADH where there is a fragment each of the monophosphate moieties can be attached to. This is not case in nucleoside di- or tri-phosphates where only one of the phosphate moieties is attached to something else.

In addition, a pyrophosphatase (or diphosphatase) produces diphosphate groups when the phosphate groups are positioned as in nucleoside triphosphates (e.g. EC 3.6.1.8, RHEA:14245: ATP + H2O = AMP + diphosphate + H+).

Regarding thiamine. It is correct thiamine (vitamin B1) is NOT identical to thymidine, and it is NOT a nucleoside. Its structure consists of an aminopyrimidine and a thiazolium ring linked by a methylene bridge, so it is not closely related to U, T or C.

 thiamine-diphosphatase activity (GO:0004787)
 Catalysis of the reaction: TPP + H2O = TMP + phosphate. (RHEA:27998)

While the above RHEA:27998 is correct, I would recommend to change the TMP abbreviation used for thiamine monophosphate, as TMP is (also) the abbreviation for thymidine monophosphate. Either do not abbreviate or use ThMP (and ThPP).

Regarding the comment #23401 (comment) I agree with @sjm41, GO:0050333 and GO:0004787 should NOT be listed under "nucleoside triphosphate phosphatase activity"

In addition, thiamine diphosphatase is a misleading name, as it implies that thiamine includes a diphosphate group, and that it produces a diphosphate group and thiamine, A better name would be thiamine diphosphate phosphatase or thiamine diphosphate phosphohydrolase (see KEGG:R00615).

[sjm41]

Thanks @kaxelsen. Our latest edits address all of your comments and I think we're on the same page :-)

[pgaudet]

Looks like everything was done here