Structural biology – Improvements in health
The need for health improvement on the African continent continues to be a pressing issue, and START’s emphasis will be on diseases such as HIV-AIDS, malaria, tuberculosis, and African horse sickness that are devastating to human and animal populations. The structural biology strand of START research will support scientists in finding and developing cures by researching and understanding the fundamental molecular structure of certain diseases. Prof. Trevor Sewell from the University of Cape Town explains:
“START will allow us to understand drug targets and cure African diseases. We will establish a collaborating network of seven South African institutions (the Universities of Pretoria, Witwatersrand, North West, Free State, Stellenbosch, Cape Town and the National Institute for Communicable Diseases) that will enable young researchers to boost medical and veterinary research”.Prof. Trevor Sewell, University of Cape Town
A START project at University of Cape Town led by co-investigator Prof Edward D Sturrock
Structural biology of angiotensin converting enzyme and related metalloproteases
Enzymes play important roles in a variety of biological processes in the human body. Angiotensin converting enzyme (ACE) for example, is a metalloprotease which regulates blood pressure and is also involved in scar tissue development (fibrosis). Conditions such as diabetes and tuberculosis can lead to excessive scar tissue formation, which ultimately stops proper organ function. Currently, there is no specific treatment for fibrosis and affected individuals have an average survival period of 2-4 years. Hypertension, on the other hand, is a major risk factor for cardiovascular disease and stroke, which accounted for 15.2 million global deaths in 2016. Our research group, led by Prof Edward Sturrock, is based in the Department of Integrative Biomedical Sciences at the University of Cape Town and has a long-standing interest in ACE and related zinc metalloproteases.
Although ACE inhibitors reduce fibrosis and are widely used for treating hypertension, certain patients experience the life-threatening side-effect of severe swelling below the skin surface of the throat and tongue. With the resources provided by START, we aim to design compounds devoid of this side-effect. Detailed structures of ACE will be solved using X-ray crystallography and cryo-electron microscopy to improve our understanding of how ACE functions and enable the design of antifibrotic and antihypertensive drugs.