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Providing a molecular mechanism for P-glycoprotein; why would I bother?

Callaghan R - Biochem. Soc. Trans. (2015)

Bottom Line: Following the binding of substrate and nucleotide, a complex series of conformational changes in the membrane and cytosolic domains translocates substrate across the membrane.Despite over 30 years of biochemical investigation, the availability of structural data and a plethora of chemical tools to modulate its function, the molecular mechanism remains a mystery.This review highlights the progress that has been achieved in understanding this complex protein and the value of undertaking molecular studies.

View Article: PubMed Central - PubMed

Affiliation: Division of Biomedical Science & Biochemistry, Research School of Biology, The Australian National University Canberra, ACT 0200, Australia.

No MeSH data available.


Related in: MedlinePlus

The frustrations of fundamental researchA schematic representation of the low-resolution structure of membrane bound P-gp to illustrate its ability to bind and transport drugs in an ATP-dependent manner. The quotation bubbles represent a ‘rogue's gallery’ of statements from grant and/or manuscript reviewers received over the years by fundamental biochemists.
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Figure 1: The frustrations of fundamental researchA schematic representation of the low-resolution structure of membrane bound P-gp to illustrate its ability to bind and transport drugs in an ATP-dependent manner. The quotation bubbles represent a ‘rogue's gallery’ of statements from grant and/or manuscript reviewers received over the years by fundamental biochemists.

Mentions: I can understand that this topic is not high on everyone's list, but why the dismissive attitude towards fundamental research displayed by this colleague? It seems that a broader disinterest, disillusionment or dislike of fundamental biochemical research has emerged in the last decade (Figure 1). Are fundamental research questions and endeavours valued anymore? Should all biomedical research have a near immediate and tangible benefit from an economic standpoint? Have scientists also become obsessed with ‘budget bottom lines’ and pre-occupied with a desire for ‘bankable projects’ and ‘translational research’? Perhaps we have lost the desire to explore and provide an understanding of complex biological phenomena without justification on economic grounds? Should we simply ignore the intricacies and complexity of the natural world and merely view it as a tool to generate profit? There is nothing wrong with translational research, but surely it cannot completely replace fundamental research. This review provides a brief (and far from exhaustive) account of how research into the molecular mechanism of P-gp has progressed since its discovery in 1976. It is important to note that the field has also benefitted greatly from equally heroic efforts with other ATP-binding cassette (ABC) proteins and transporters from distinct families. This review cannot provide a wide sweep of these efforts and is restricted to studies exclusively with P-gp. Progress has been slow at times but the timeline demonstrates the creativity, resourcefulness, stirring debate and co-operation of scientists in the field. Hopefully it will provide an answer to the question posed by my colleague!


Providing a molecular mechanism for P-glycoprotein; why would I bother?

Callaghan R - Biochem. Soc. Trans. (2015)

The frustrations of fundamental researchA schematic representation of the low-resolution structure of membrane bound P-gp to illustrate its ability to bind and transport drugs in an ATP-dependent manner. The quotation bubbles represent a ‘rogue's gallery’ of statements from grant and/or manuscript reviewers received over the years by fundamental biochemists.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4613492&req=5

Figure 1: The frustrations of fundamental researchA schematic representation of the low-resolution structure of membrane bound P-gp to illustrate its ability to bind and transport drugs in an ATP-dependent manner. The quotation bubbles represent a ‘rogue's gallery’ of statements from grant and/or manuscript reviewers received over the years by fundamental biochemists.
Mentions: I can understand that this topic is not high on everyone's list, but why the dismissive attitude towards fundamental research displayed by this colleague? It seems that a broader disinterest, disillusionment or dislike of fundamental biochemical research has emerged in the last decade (Figure 1). Are fundamental research questions and endeavours valued anymore? Should all biomedical research have a near immediate and tangible benefit from an economic standpoint? Have scientists also become obsessed with ‘budget bottom lines’ and pre-occupied with a desire for ‘bankable projects’ and ‘translational research’? Perhaps we have lost the desire to explore and provide an understanding of complex biological phenomena without justification on economic grounds? Should we simply ignore the intricacies and complexity of the natural world and merely view it as a tool to generate profit? There is nothing wrong with translational research, but surely it cannot completely replace fundamental research. This review provides a brief (and far from exhaustive) account of how research into the molecular mechanism of P-gp has progressed since its discovery in 1976. It is important to note that the field has also benefitted greatly from equally heroic efforts with other ATP-binding cassette (ABC) proteins and transporters from distinct families. This review cannot provide a wide sweep of these efforts and is restricted to studies exclusively with P-gp. Progress has been slow at times but the timeline demonstrates the creativity, resourcefulness, stirring debate and co-operation of scientists in the field. Hopefully it will provide an answer to the question posed by my colleague!

Bottom Line: Following the binding of substrate and nucleotide, a complex series of conformational changes in the membrane and cytosolic domains translocates substrate across the membrane.Despite over 30 years of biochemical investigation, the availability of structural data and a plethora of chemical tools to modulate its function, the molecular mechanism remains a mystery.This review highlights the progress that has been achieved in understanding this complex protein and the value of undertaking molecular studies.

View Article: PubMed Central - PubMed

Affiliation: Division of Biomedical Science & Biochemistry, Research School of Biology, The Australian National University Canberra, ACT 0200, Australia.

No MeSH data available.


Related in: MedlinePlus