CHEM2052 Tutorial Example4

CHEM2052_Tutorial_Example4

spinqualitylabelsall models Renin (PDB code 2i4q) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Chem2052: Example 3 - Serine Proteases Serine proteases account for over one-third of all known proteolytic enzymes ,. Within the diverse collection of serine proteases, the most famous members are trypsin, chymotrypsin and elastase. Aside from their key roles in digestion (and other physiological processes) , the unique specificities of these enzymes make them useful tools in biochemistry and molecular biology to ascertain protein sequences. Looking at the structures below, it is apparent that these three enzymes have similar folds. This conservation of tertiary structure is due to extensive similarities at the level of primary amino acid sequence. However, there are small differences in amino acid sequence among the proteins, which are reflected in their different specificities. Each protein cleaves the peptide backbone after (or on the carbonyl side) of a specific type of sidechain. After examining the molecular basis for these functional similarities and differences, you will hopefully see why serine proteases are a classic example of how structure dictates function! Chymotrypsin Trypsin Elastase Active Sites Renin Catalytic Residues Background In later lecture we will look at an enzyme called Renin (also known as angiotensinase). This enzyme is involved in a biological pathway leading to elevation of blood pressure, which can be beneficial in many ways. However if this process has become overactive, hypertension (high blood pressure) can result. Hypertension leads to cardiovascular disease which is the leading cause of death globally. The World Health Organisation states "An estimated 17.3 million people died from cardiovascular disease in 2008, representing 30% of all global deaths" see the following web page if you want to know more: [1]. Since the 1970s Renin Wikipedia Site scientists have been trying to modulate the action of renin by blocking the active site of the enzyme and preventing its function, hence lowering blood pressure. Aliskerin is the only renin inhibitor in clinical use today. However there is still interest in developing new, improved inhibitors. This question looks at a renin inhibitor identified through research at Pfizer. Structural highlights This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

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