KinasePro

Kinase Chemistry – Just a year and a half behind the times.

CH——-Pi

Posted by kinasepro on October 23, 2008

Kissei’s done a little math on LCK ligands and suggests the stablization owes to those methyl’s.

BMCL

Cool, yah ,so, umm, like, thats why they gotta be flat.

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8 Responses to “CH——-Pi”

  1. Ed said

    Dude your link to the BMCL seems busted.

  2. kinasepro said

    darned those DOIs sometimes… Try it now

  3. Milo said

    I am clearly not an expert in the field…. but…. is it reasonable to say that there is this tiny, weak, almost not-there interaction at work based on calculations from a structure that may or may not accurately represent the biological conformation of the protein? This seems like a huge stretch here.

    How is this different than a simple dipole/quadripole interaction?

  4. kinasepro said

    I’m not qualified to comment on the calculations… And while there are two strikes going against this paper (a) its a BMCL, and (b) the images are mickeymouse, I still do believe that there could well be some form of attractive force at play here.

    ATP and Kinase ligands are darn near exclusively flat in this region, not just this one structure, but hundreds of others as well. Doesn’t seem like a stretch to think its due to the LUE’s and VAL’s and ILE’s you often find flanking the purine in ATP, or your fugly insoluble inhibitors.

  5. Anonymous said

    I’ve not read the paper so don’t know whether they made mutants to test their hypothesis?

  6. Will comment on the calculations later. Wanted to let you know about the latest Shokat dual Tyrosine/PI3K ‘rationally’ designed inhibitor and the explanation of its specificity. That is, if the all-knowing KP hasn’t already seen it.
    Nature Chem. Biol. doi:10.1038/nchembio.117

  7. fromsgc said

    Of course he does! 🙂

    https://kinasepro.wordpress.com/2008/10/14/plethora-o-pdbs/

  8. kinasepro said

    Yep, saw the PDB’s which published before the paper, thanks for the heads up.

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