Major step to unravelling the structure of membrane-bound proteins published in Nature journal.

In their pursuit of knowledge on cell biology, a group of international researchers has elucidated the structure of a bacterial cell membrane enzyme, which may one day contribute to unravelling new mechanisms to target a variety of diseases. One of the contributing researchers is South African biochemist, Dr Colin Kenyon, who has joined a handful of researchers at the CSIR to be published in the prestigious Naturejournal. Kenyon, a principal researcher and CSIR Biosciences Fellow, contributed to an article titled, Crystal structure of the integral membrane diacylglycerol kinase, which was published in Nature’s online edition at www.nature.com on 15 May 2013.

Kenyon was approached by Prof Martin Caffrey, an expert in the field of the structure of membrane proteins at the School of Biochemistry and Immunology at Trinity College, Dublin in Ireland, on the basis of work Kenyon and his colleagues at the CSIR had published earlier. Kenyon’s research relates to the study of reaction mechanisms of proteins called kinases, and how these proteins use adenosine triphosphate (ATP), a molecule which is the energy currency of cells.  Kinases play a pivotal role in cellular metabolism and regulation, and therefore represent 20-30% of all targets in serious drug discovery programmes, for example, targeting the treatment of cancer and diseases such as malaria, tuberculosis and other bacterial infections.

Historically, it has been difficult to determine the three-dimensional structure and function of membrane-bound proteins, information which is essential for this research. Researchers normally use X-ray crystallography to determine the structure of proteins, but membrane-bound proteins are situated in lipids, which means that they are hydrophobic – literally meaning ‘water fearing’. If extracted, they unravel and lose their structure. Thanks to groundbreaking research by teams such as the group headed by Caffrey, techniques are now being developed to determine the X-ray structure of crystallised membrane proteins.

Kenyon and his colleagues were requested to help define the functionality of the newly crystallised diacylglycerol kinase (a bacterial membrane enzyme), which Caffrey and his colleagues were studying. The group presented a crystal structure for three functional forms of the bacterial membrane enzyme.

“The membrane proteins are a potentially vast untapped source of new targets in drug discovery,” Kenyon says.

Nature’s impact factor is 36,28; this is a measure of how many times a journal generates citations in other work as measured by the Thomson Institute of Scientific Information. This is among the highest of any science journal and there is great competition among scientists to have their work published there. For most researchers, this type of publication is not only about the prestige of publishing in this specific journal, but also the credence it brings to years of exploratory research.