[Go] Advice on adding an enzyme function

Thu May 22 09:23:27 PDT 2008

On May 22, 2008, at 8:53 AM, D'Eustachio, Peter wrote:

> 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.

Good example!  Which brings to mind all the restriction-modification  
systems in bacteria: There are a very large number of possible  
recognition sequences and positions for the cleavage/modification site  
relative to the recognition sequence, and separate GO terms for each  
seems like massive overkill to me.

Jim

>
>
> 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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=====================================
Jim Hu
Associate Professor
Dept. of Biochemistry and Biophysics
2128 TAMU
Texas A&M Univ.
College Station, TX 77843-2128
979-862-4054

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