Structural and biochemical insights into two key metabolic pathway enzymes

The major aspect of climate change is global warming in which the average temperature of the Earth’s climate system is rising over the long-term due to the increase of greenhouse gases such as carbon dioxide. The global warming effects are rising sea levels, extreme weather, ocean acidification, and environmental impacts such as species ecosystem change like coral bleaching. For instance, a pathogenic bacterium uses dimethylsulfoniopropionate (DMSP) as a cue to attack heat stressed coral. DMSP plays an important role in the global sulfur cycle and a key element in the marine food web. It is the precursor of climatically active gas dimethyl sulfide (DMS) and an industrial valuable compound acrylate. The enzymes break down DSMP and generate 10 million tons of DMS annually. While acrylate is of great importance in paint and plastic industry, DMS is the major source of cloud-condensation nuclei (CCN) over the oceans. CCN is produced by oxidation of DMS and the CCN population controls albedo and consequently the Earth’s temperature. The biological regulation of DMS affects global warming and increasing CCN population will decreases the temperature and counteract the warming due to atmospheric carbon dioxide. Herein this study we examined and investigated the structural and chemical properties of a highly active enzyme (DddL) in marine bacteria that is responsible for DMSP breakdown to DMS and acrylate. We solved the crystal structure of enzyme and proposed the mechanism by which DddL converts DMSP to DMS and acrylate on atomic level. The knowledge of these biochemical and mechanistic studies will assist us to better understand the biological regulation of global warming and will aid in developing economically viable methods for renewable acrylate production.

Tens of millions of people have been diagnosed with cancer each year and in many countries. It is the second most common cause of death. Cancer is a disease which some of the body’s cells begin to divide without stopping and spreads into the surrounding tissues. Glycolysis (glucose degradation) is a metabolic pathway which converts glucose into pyruvate. Pyruvate enters into the mitochondria, which is the cells powerhouse in our body. Normal cells primarily produce their energy through highly efficient pathway via mitochondria. While the cancerous cells predominantly obtain their energy from less-efficient pathway with high rate of glycolysis. There are many enzymes that regulate the glycolysis pathway and play an important role in altered metabolism in cancerous cells. In this study we investigated an enzyme called pyruvate kinase muscle 2 (PKM2). PKM2 exists in a high-activity tetrameric form in normal cells and a low-activity dimeric form in cancerous cells. Dimeric form of PKM2 benefits cancer cells by slowing down the rate of glycolysis and providing building block of macromolecules, which are necessary for rapid growth of cancerous cells. We examined PKM2 and its variants in order to further understand the regulation and function of PKM2 in production of tumors. PKM2 is considered as a potential target for cancer diagnosis and treatment.