Allosteric modulation of H-Ras GTPase: Difference between revisions

'''H-Ras''' is a small monomeric GTPase protein that is found inside of cells.  It helps regulate cell division in cells through signal transduction pathways such as the Raf-MAPK pathway.  H-Ras is also known as a molecular switch, it contains two switch regions: Switch I and Switch II.  Switch I is regions 32-40, Thymine 35 plays an important role in switch I region and switch II is regions 60-76, Glycine 60 plays an important role for switch II region.  Both of these switches depend on the phosphate group on a GTP molecule to turn “on” and “off”. In the Ras catalytic cycle, Ras is activated when it binds to a GTP molecule turning both switch regions “on”.  This pathway also involves GTPase activating protein, which catalyzes the hydrolysis of the GTP molecule that is bound to  Ras causing the switches to turn “off”. Ras was first discovered in a retrovirus which was known to cause saracoma in rats hence the name "ras" "rat saracoma"

H-Ras is 166 Amino Acids long with six beta sheets and six helices.  One of the helix 2 is a 3/10 helix, unlike the rest of the helices.  Also it contains a Calcium Acetate in the allosteric binding site that is located by the Loop 7 and Helix 3.  The structure of Ras actually forms slightly different when it is and isn't bound to calcium acetate.  The GTP molecule will then attach on the bottom of the protein inbetween the Switch I and Switch II region. The switch I and switch II regions change conformation between their active and inactive state.  This change in conformation of the switch regions helps other proteins determine whether the Ras protein is active or inactive.  Add more about binding of calcium acetate and how it bends the loop 7 and helix 3 to allow switch I and switch II to bind to the GTP molecule [[Image:Ras calcium acetate and gppNHp2.jpg|thumb|400px|center|Calcium Acetate/Loop 7/Helix 3/GppNHp]] [[Image:Tileshop.jpeg|thumb|400px|right|Allosteric modulation of calcium acetate on Ras protein]] [[Image:Active and inactive.jpg|thumb|800px|left|Active and Inactive Ras protein]]