Actin up with decavanadate

Recent work at Diamond has unveiled the way in which an intriguing potential new drug interacts with actin, an abundant protein found in all cells. 

Vanadium is a trace element that is found in animals and plants, but its exact role in humans remains elusive. Compounds that contain vanadium are involved in diabetes control and bone remodelling, and also possess anti-cancer and antibacterial properties, so it is no surprise that further efforts are underway to unlock the full pharmacological potential of vanadium.

     

Decavandate is one such compound that contains vanadium, ten atoms of it in fact. It is a type of compound known as a polyoxometalate (POM), which is used for a wide variety of applications such as catalysis, preventing corrosion and protein crystallisation. More interestingly, decavandate interacts with a number of proteins in our bodies, namely actin.

Actin is an essential protein that is needed to maintain the structural integrity of cells, and it also plays a large role in cell division. Upon meeting actin, decavanadate prevents it from assembling into fibres and thereby stops it from functioning normally. This destructive ability could be harnessed to counter cancer, which is very reliant on processes involving actin such as speedy cell division and metastasis.

To understand the interplay between decavanadate and actin, a team of scientists from Portugal, with help from Dr Diego Gianolio, Beamline Scientist at B18, set out to explore the molecular processes that lead to actin inhibition.

The team combined two techniques at B18 at Diamond Light Source: EXAFS (extended X-ray absorption fine structure) and XANES (X-ray absorption near-edge structure) and watched what happened to both molecules under different conditions.

They amazingly identified the exact spot where decavanadate interacted with actin, a discovery never before seen. With this new information, it is hoped that the reasons behind decavanadate’s remarkable anti-cancer and antibacterial properties can be revealed. The ultimate aim is to develop novel medicines containing vanadium that will have impressive abilities at inhibiting proteins.

Dr Gianolio concluded, “These findings have important consequences for the understanding, at a molecular level, of the significant biological activities of decavanadate and similar polyoxometalates, aiming at potential pharmacological applications.”
 

Related publication:

M Paula et al. An EXAFS Approach to the Study of Polyoxometalate–Protein Interactions: The Case of Decavanadate–Actin. Inorganic Chemistry 2017 56 (18), 10893-10903. DOI: 10.1021/acs.inorgchem.7b01018