Dear BB
For my one cent's worth, I think it is simpler if the residue name in the coordinate set matches that in the sequence deposition for the protein (and DNA) - i.e. before any post-translational modification is carried out. Whether a particular modification is actually present or absent may depend on the organism (or even the cell line) in which the protein was expressed… which is seldom the natural one.
best wishes
Pete
On 9 Jul 2013, at 16:21, [log in to unmask] wrote:
> Dear Marc (and BB),
>
> I guess as usual, in real life the obvious is less obvious as it seems to be. I, and I guess many of my colleagues trying to find new drugs, have quite a few protein-inhibitor complexes where the inhibitor formed a covalent link with e.g. the active site serine. In these cases, I am perfectly happy with having the inhibitor being defined as a separate group, linked via a LINK record. For me, it does not make sense to treat these covalent inhibitors differently from noncovalent inhibitors.
>
> In the end, I guess, it will boil down to some arbitrary choice, either imposed upon us by the pdb, or individually taken by the crystallographer who produced the crystal structure.
>
> My 2 cts,
> Herman
>
>
> -----Ursprüngliche Nachricht-----
> Von: CCP4 bulletin board [mailto:[log in to unmask]] Im Auftrag von Mark J van Raaij
> Gesendet: Dienstag, 9. Juli 2013 16:23
> An: [log in to unmask]
> Betreff: Re: [ccp4bb] modified amino acids in the PDB
>
> - really the only complicated case would be where a group is covalently linked to more than one amino acid, wouldn't it? Any case where only one covalent link with an is present could (should?) be treated as a special amino acid, i.e. like selenomethionine.
> - groups without any covalent links to the protein are better kept separate I would think (but I guess this is stating the obvious).
>
> Mark J van Raaij
> Lab 20B
> Dpto de Estructura de Macromoleculas
> Centro Nacional de Biotecnologia - CSIC
> c/Darwin 3
> E-28049 Madrid, Spain
> tel. (+34) 91 585 4616
> http://www.cnb.csic.es/~mjvanraaij
>
>
>
>
>
> On 9 Jul 2013, at 12:49, Frances C. Bernstein wrote:
>
>> In trying to formulate a suggested policy on het groups versus
>> modified side chains one needs to think about the various cases that
>> have arisen.
>>
>> Perhaps the earliest one I can think of is a heme group.
>> One could view it as a very large decoration on a side chain but, as
>> everyone knows, one heme group makes four links to residues. In the
>> early days of the PDB we decided that heme "obviously" had to be
>> represented as a separate group.
>>
>> I would also point out that nobody would seriously suggest that
>> selenomethionine should be represented as a methionine with a missing
>> sulfur and a selenium het group bound to it.
>>
>> Unfortunately all the cases that fall between selenomethionine and
>> heme are more difficult. Perhaps the best that one must hope for is
>> that whichever representation is chosen for a particular case, it be
>> consistent across all entries.
>>
>> Frances
>>
>> P.S. One can also have similar discussions about the representation of
>> microheterogeneity and of sugar chains but we should leave those for
>> another day.
>>
>> =====================================================
>> **** Bernstein + Sons
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>> * * ***
>> **** * Frances C. Bernstein
>> * *** [log in to unmask]
>> *** *
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>> =====================================================
>>
>> On Tue, 9 Jul 2013, MARTYN SYMMONS wrote:
>>
>>> Hi Clemens
>>> I guess the reason you say 'arbitrary' is because there is no
>>> explanation of this rule decision?
>>> It would be nice if some rationalization was available alongside the values given.
>>> So a sentence along the lines of 'we set the number owing to the
>>> following considerations' ?
>>> However a further layer of variation is that the rule does not seem
>>> to be consistently applied
>>> - just browsing CYS modifications:
>>> iodoacetamide treatment gives a CYS with only 4 additional atoms
>>> but it is split off as ACM.
>>> However some ligands much larger than 10 residues have been kept
>>> with the cysteine ( for example CY7 in 2jiv and NPH in 1a18.
>>> My betting is that it depends on whether something has been seen
>>> 'going solo' as a non-covalent ligand previously so that it pops up
>>> as an atomic structural match with a pre-defined three-letter code.
>>> This would explain for example the ACM case which you might expect
>>> to occur in a modified Cys. But it has also been observed as a
>>> non-polymer ligand in its own right so goes on as a separate modification?
>>> However to be honest I am not sure I have ever seen the rationale
>>> for this written down.
>>> 'Non-polymer' heterogens can turn up either linked or not. Once
>>> they are in the residues they have to make a call on which kind of
>>> backbone they will feature in within the pdb.
>>> That is why there is 'D5M' for non-polymer deoxyAMP. Also known as
>>> ' DA' when it is 'DNA-linking' but so far not fessing up to life
>>> under a third code as 'RNA-linking'....
>>> Now is perhaps the time to ask for explanations of these nomenclature
>>> features before they become hard-wired in the new pdb deposition
>>> system (however there may be time - I refer you to my previous posting ;).
>>>
>>> Cheers
>>> Martyn
>>>
>>> Dr Martyn Symmons
>>> Cambridge
>>> _____________________________________________________________________
>>> ________________
>>> From: Michael Weyand <[log in to unmask]>
>>> To: [log in to unmask]
>>> Sent: Monday, 8 July 2013, 10:03
>>> Subject: [ccp4bb] modified amino acids in the PDB Dear colleagues, We
>>> deposited protein structures with modified lysine side chains and
>>> were surprised that the PDB treats the modification as an independent
>>> molecule, with a ?LINK? record indicating the covalent bond ? instead
>>> of defining a modified residue (that?s what we had uploaded to the PDB).
>>> Apparently, anything attached to an amino acid is considered an
>>> independent molecule (and the lysine just called a regular lysine) if
>>> it comprises more than 10 atoms (see below for the PDB guidelines).
>>> I think that?s kind of arbitrary and would give all modified residue
>>> also modified names ? i.e. individual names for all modified lysines,
>>> as it is done for acetyl- or methyl-lysines, for example. I wonder
>>> what other people?s opinion is?!
>>> Best regards
>>> Clemens
>>> ---------------------------------------------------------------------
>>> ---------------
>>> ------------
>>> This is in accordance to the wwPDB annotation guidelines
>>> (http://www.wwpdb.org/procedure.html#toc_2).
>>> "*Modified amino acids and nucleotides* If an amino acid or
>>> nucleotide is modified by a chemical group greater than 10 atoms, the
>>> residue will be split into two groups: the amino acid/nucleotide
>>> group and the modification. A link record will be generated between
>>> the amino acid/nucleotide group and the modification. For modified
>>> amino acids and nucleotides that were not split will follow standard atom nomenclature."
Prof Peter Artymiuk
Krebs Institute
Department of Molecular Biology & Biotechnology
University of Sheffield
Sheffield
S10 2TN
ENGLAND
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