[Go] Advice on adding an enzyme function

[Benjamin Hitz]

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