Hi Faisal, Lots of enzymes aren't too picky when it comes to nucleotide cofactors - depending on their physiological role, they may or may not select for high specificity. I'd encourage you to think about the opposite question - why are some enzymes highly specific for particular nucleosides? What controls that specificity? And what makes your enzyme different from those ones? That might help you identify the factors at play in your case.
It's not C/T nucleosides, but I'll plug my colleague's paper studying an enzyme that binds both GTP and ATP, where he showed how the enzyme could accommodate both in the active site: http://www.ncbi.nlm.nih.gov/pubmed/22371504 That said, there's a lot of literature out there on nucleobase recognition - I'd suggest you dive in. Also, just to check, both of your substrates have the same sugar, correct? Are they both deoxyribonucleosides, or ribonucleosides? Because that would be the first place to look, if you haven't already. Shane Caldwell McGill University On Thu, May 28, 2015 at 8:12 AM, Faisal Tarique <faisaltari...@gmail.com> wrote: > Hello everyone > > I am working on a 5'-nucleotidase (Mg as a cofactor) and have a decent > structure of the same at 2A resolution..While doing its biochemical > characterization i found it hydrolyzing TMP: Thymine-5’-monophosphate at > much higher rate than CMP Cytosine-5’-monophosphate (40 fold difference). > Since the structure of TMP and CMP are very similar what could be the > possible explanation for this difference or how one should approach to > explain this difference..Can modelling, docking and energy minimization > give an insight into this direction, if yes then what parameters should be > looked into..To summarize..Theoretically how it is possible to explain this > difference..?? > > Thanks in advance > > -- > Regards > > Faisal > School of Life Sciences > JNU > >
