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:[email protected]] Im Auftrag von Mark J van Raaij Gesendet: Dienstag, 9. Juli 2013 16:23 An: [email protected] 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 > * * Information Systems Consultants > **** 5 Brewster Lane, Bellport, NY 11713-2803 > * * *** > **** * Frances C. Bernstein > * *** [email protected] > *** * > * *** 1-631-286-1339 FAX: 1-631-286-1999 > ===================================================== > > 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 <[email protected]> >> To: [email protected] >> 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."
