My work being centered around structure based drug design,I have always wonder what might be the exact reason behind the unavailability of structural model of human COX 2 (gene PTGS2). By that I specifically mean experimental crystallographic solved models. There is abundant structural models of cox 2 from ovine and murine origin in PDB, but there is no cox 2 model of human origin (except homology model PDBID: 1V0X). Availability of crystallographic model of COX2 from human can significantly improve drug development concerning human anti-inflammatory research and development of effective Non-Steroidal Anti-Inflammatory Agents .
Any wild guess from crystallography cons about explanation regarding what is exact difficulty in solving cox2 structure from human origin?
There could be a number of issues, the first could that no-one has tried as related structures have been solved. Since this an important drug target it would seem likely that people have tried and failed. Human protein structures are often much more difficult than bacterial since problems can arise with protein folding (lack of appropriate chaperones in overexpression system), post translational modification etc..... see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938586/ and references in for more info. Hopefully someone is solving it as we speak and it will soon be published.
This paper (www.nature.com/nsmb/journal/v3/n11/abs/nsb1196-927.html) claims to have solved the first crystal structure of human COX-2. However, the model coordinates were either not deposited in the PDB or were never released. One possible reason could be an intellectual property issue as the structures were solved in a pharmaceutical company. The real answer can only be sought from the authors. Anyways, one can always try to reproduce the results by following the methods suggested in the paper.
@ Avinash S. Punekar
I have read the paper you suggested. And you are right, the coordinates were not deposited in PDB, since their paper do not mention any PDB ID or any statement of deposition in PDB. Thank you for clearing my doubt... or else I would have kept thinking that this structure is still unsolved.
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