The current progress in biomedical science works on the basis of the identification of a gene, a protein, a biochemical function and a biological activity followed by a possible drug identification processing. This information seems to be in a linear cascade. Many Biotechs have invested on this linear cascade billions of dollars.
A typical example of a protein is the CREB-binding protein CREBBP or CBP, which is a Histone Acetyltransferase and might be used as a “scaffold” in protein complexes. Is the biological property of CBP a copy-paste expression of its enzymatic activity? Does the presence of CBP in a complex a reflection of CBP enzymatic activity or the presence of a protein in a complex remodifies its biological activities?
In fact do we search an obstacle in many drug screening assays when testing enzymatic activities that are far representative of the real biological property of the target protein in a specific biological/topological environment?
dear Vassilis,
with this interesting question we fall in the realm of the harsch dispute between reductionism and emergentism. The most recent philosophical proposals (I'm thinking about Bechtel) talk about "New Mechanist" theories, which state about intertwined levels, conditioning one each other. In your case, the enzymatic activity infuences the biological acrivity which, in turn, influences the enzymatic activity.
Dear Arturo,
You are the best!
I am working on the topological role of the protein functions and be back to you very soon!
In fact, for drug screening might be best to use a Topological Space (Choros) rather than an enzymatic activity. Geometry could resolve many biological questions and make drug screening faster and more reliable.
What we need to identify is the dimensional properties of Choros.
best, vassilis
Lens crystallins constitute another interesting example of the difficulty of making a distinction between structural and enzymatic functions of proteins.
https://en.wikipedia.org/wiki/Crystallin
Dear Adam,
Thanks for this valuable information on lens crystallins. This is indeed a very nice and intriguing example.
I was thinking also for the big family of nuclear hormone receptors that are representative factors of transcription under ligand control. In fact, many example emphasize that their biological activities are often DNA-binding independent and thought their positioning into a specific topology/complex domain might influence their function upon signal activation – a biological function that is far different of their transcription potential. Another example are the Ubiquitination enzymes, the E3 ligases that could express parallel activities and so on.
I think that the "New Mechanist" theories as Arturo said may have dramatic application in modern biology and mainly in new drug screening systems. We need to be efficient in cancer and other anti-drug therapies so to use intelligent models in order to obtain solid answers. I do not think that using a linear processing even if this is a kinase activation and their inhibitors in a cell system and, in parallel a library of potential drugs could effectively come out something very accurate in drug screening. In this kind of assays we miss valuable biological information and this is the Topological space/complex domains – what I called Choros.
The presentation of additional examples where enzymatic activities/structural propterties – and biological function are separate entities could be of interest so to obtain a global view of our biological system. Your contribution is welcome. Thanks.
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