[Go] Advice on adding an enzyme function
D'Eustachio, Peter
Peter.D'Eustachio at nyumc.org
Thu May 22 06:53:22 PDT 2008
Proteases look like they will be a good use case here - they raise
exactly the issues of how to define substrate specificity (and how to
know whether it's been defined correctly), and how (or whether it's
possible) to use specificity to distinguish functional classes of
enzymes and preserve an acceptable level of generality.
Peter
-----Original Message-----
From: go-bounces at genome.stanford.edu
[mailto:go-bounces at genome.stanford.edu] On Behalf Of Benjamin Hitz
Sent: Wednesday, May 21, 2008 4:47 PM
To: Alexander Diehl
Cc: GO List
Subject: Re: [Go] Advice on adding an enzyme function
On May 21, 2008, at 10:29 AM, Alexander Diehl wrote:
> I agree if there is no difference in the mechanism of catalysis that
> we should not create substrate specific terms. However, selectivity
> among classes of substrates suggests mechanistic differences to me.
I don't think this is the case, Alex. It's often more of a binding
site size (or other characteristic) issue than chemical mechanism.
I suppose the answer is that substrate specific terms should be added
"sometimes".
In this case (spermine/spermidine) I would say it's probably not a
huge deal that some of the enzymes work on substrates other than
spermine and spermidine. I am pretty sure that it shouldn't matter if
they are proK vs. euke, because we should try to avoid inserting
evolutionary arguments.
Ben
>
>
> Rama Balakrishnan wrote:
>> I am not very enthusiastic either about substrate specific terms.
>> I am not sure if we have consistently added substrate-specific
>> terms. Long time back (really long time back) I was told that if
>> the mechanism of catalysis is the same between substrates, then we
>> don't want to create substrate specific terms.
>>
>> Rama
>>
>> On May 21, 2008, at 9:26 AM, Jim Hu wrote:
>>
>>> Hi guys,
>>>
>>> I'm not enthusiastic about substrate-specific child terms. There
>>> are too many possible substrates and it seems like this would be
>>> better as a with CheBI. Substrate class specific child terms,
>>> sure - leaving aside what makes a group of substrates members of a
>>> class. I'd also hate to get bogged down in arguments about
>>> whether a particular substrate is physiologically significant.
>>>
>>> Jim
>>>
>>> On May 21, 2008, at 10:48 AM, Pankaj Jaiswal wrote:
>>>
>>>> I support substrate-specific child terms for catalytic
>>>> activities. It makes a lot of sense not only in species specific
>>>> annotation but also in spatio-temporal functions as well, because
>>>> the same molecules can use different substrates in different time
>>>> and space in the same organism.
>>>>
>>>> Pankaj
>>>>
>>>> Alexander Diehl wrote:
>>>>> Jane,
>>>>> There is precedent in the GO for such substrate-specific child
>>>>> terms, for instance, 'xanthoxin dehydrogenase activity ; GO:
>>>>> 0010301' is a child of 'alcohol dehydrogenase activity ; GO:
>>>>> 0004022' and 'sirohydrochlorin ferrochelatase activity ; GO:
>>>>> 0051266' and 'ferrochelatase activity ; GO:0004325'. There are
>>>>> many other examples.
>>>>> However, perhaps Harold or others with strong backgrounds in
>>>>> biochemistry will have a different bias (it's only 7 am EDT
>>>>> right now)
>>>>> Thanks,
>>>>> Alex
>>>>> Jane Lomax wrote:
>>>>>> Hi Alex - both the euk and prok enzymes act on spermine and
>>>>>> spermidine, but the euk enzyme also acts on a range of other
>>>>>> alkane-alpha,omega-diamine substrates including putrescine and
http://dev.gramene.org/db/markers/marker_view
>>>> http://dev.gramene.org/db/markers/marker_view
>>>>>> 1,3-diaminopropane. In an assay, the prok enzyme does not act
>>>>>> on putrescine and 1,3-diaminopropane.
>>>>>>
>>>>>> So I think you're suggesting I add child terms to GO:0004145,
>>>>>> such as 'spermine N-acetyltransferase activity' etc?
>>>>>>
>>>>>> Jane
>>>>>>
>>>>>>
>>>>>> Alexander Diehl wrote:
>>>>>>> Jane,
>>>>>>>
>>>>>>> I would vote no, if the following conditions are true:
>>>>>>>
>>>>>>> 1) When presented with any of the eukaryotic substrates, the
>>>>>>> prokaryotic enzyme catalyzes the same reaction as the
>>>>>>> eukaryotic one.
>>>>>>>
>>>>>>> 2) When presented with any of the prokaryotic substrates, the
>>>>>>> eukaryotic enzyme catalyzes the same reaction as the
>>>>>>> prokaryotic one.
>>>>>>>
>>>>>>> When you say that the prokaryotic enzyme acts on a different
>>>>>>> range of alkane-alpha,omega-diamine substrates, do you mean
>>>>>>> that it has a different range of substrates available in the
>>>>>>> organisms where it is found, or that it cannot act upon the
>>>>>>> substances found in eukaryotic organisms.?
>>>>>>>
>>>>>>> If the latter is true, I would vote yes, and create substrate
>>>>>>> specific terms for GO:0004145.
>>>>>>>
>>>>>>> -- Alex
>>>>>>>
>>>>>>>
>>>>>>> Jane Lomax wrote:
>>>>>>>> Hi - do we have any guidelines anywhere for when to add an
>>>>>>>> enzyme function term or not? I had a look on the wiki and in
>>>>>>>> the documentation and couldn't see anything. If not, perhaps
>>>>>>>> we should add something - it seems that there have been quite
>>>>>>>> a few discussions in this area and might be good to capture
>>>>>>>> it all somewhere.
>>>>>>>>
>>>>>>>> Anyhow, my dilemma is this - we have a term 'diamine N-
>>>>>>>> acetyltransferase activity ; GO:0004145' which has EC
>>>>>>>> 2.3.1.57. The EC is based on the eukaryotic enzyme, and the
>>>>>>>> reaction catalysed is: acetyl-CoA + an alkane-alpha,omega-
>>>>>>>> diamine = CoA + an N-acetyldiamine. Several different
>>>>>>>> substrates (i.e. alkane-alpha,omega-diamines) are acted upon.
>>>>>>>>
>>>>>>>> The equivalent prokaryotic enzyme has essentially the same
>>>>>>>> reaction, *but* acts on a different range of alkane-
>>>>>>>> alpha,omega-diamine substrates.
>>>>>>>>
>>>>>>>> So should I add a new term for the prokaryotic function or not?
>>>>>>>>
>>>>>>>> thanks,
>>>>>>>>
>>>>>>>> Jane
>
>
> --
> Alexander Diehl, Ph.D.
> Senior Scientific Curator
> Mouse Genome Informatics
> The Jackson Laboratory
> 600 Main Street
> Bar Harbor, ME 04609
>
> email: adiehl at informatics.jax.org
> work: +1 (207) 288-6427
> fax: +1 (207) 288-6131
>
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--
Ben Hitz
Senior Scientific Programmer ** Saccharomyces Genome Database ** GO
Consortium
Stanford University ** hitz at genome.stanford.edu
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