Structural Biology and Its Applications to the Health Sciences

• Main Authors: Aaron J Oakley, Albert Ketterman, Matthew Cj Wilce
• Other Authors: The Pennsylvania State University CiteSeerX Archives
• Format: Text
• Language: English
• Published: 2001
• Subjects: Sickle; Sperm whale
• Online Access: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1048.2721; http://neuron.mefst.hr/docs/CMJ/issues/2001/42/4/11471188.pdf

Part of the decipherment of genomic information lies in understanding the structure and function of the protein products of these genes. Protein structure is of further importance because of the molecular basis of many diseases. Structural biology is the field of research focusing on the experimental determination of the structure of biological molecules. We review the field of structural biology and its application to medical research and drug discovery, and describe the structural results recently obtained in our laboratory for the detoxifying enzyme glutathione S-transferase from the Asian mosquito Anopheles dirus species B, an important malaria vector. These enzymes have detoxifying activity toward pesticides and thus contribute to pesticide resistance in insects. Since the first protein structure (of sperm whale myoglobin) was determined (1) and Watson and Crick discovered the double helix structure of DNA (2), there has been an ever-increasing research effort in the field of structural biology. Broadly, structural biology is defined as the investigation of the structure and function of biological systems at the molecular level. The significance of this field of research in part derives from the fact that macromolecular structure is important to many disease states. Sickle-cell anemia was recognized to be a result of a mutation in hemoglobin, causing it to polymerize into long rod-shape complexes that distort and destroy red blood cells (3). The structural consequence of this mutation is now understood (4). Today, many molecular diseases, such as cancer, are known to result from mutations of genes that affect the gene product, altering its function. This is invariably caused by changes in the structure and function of the protein product of the gene. Understanding these processes can be important for treating the disease. Information about protein structure can be used in so-called structure-based drug design, where a macromolecular structure is used as a template for drug design. This review examines the ...