the change in charge distribution makes the GTP substrate more like the products of the reaction, GDP and monophosphate, this, along with opening the molecule for nucleophilic attack, lowers the transition state energy barrier of the reaction and allows GTP to be hydrolyzed more readily. GAPs, then, work to enhance the GTP hydrolysis reaction of the G proteins. By doing so, they accelerate the G protein's built-in timer, which inactivates the G proteins more quickly, and along with the inactivation of GEFs, this keeps the G protein signal off. GAPs, then, are critical in the regulation of G proteins. Specificity to G proteins In general, GAPs tend to be pretty specific for their target G proteins. The exact mechanism of target specificity is not fully known, but it is likely that this specificity comes from a variety of factors. At the most basic level, GAP-to-G protein specificity may come simply from the timing and location of protein expression. RGS9-1, for example, is specifically expressed in the rod and cone photoreceptors in the eye retina, and is the only one to interact with G proteins involved in phototransduction in this area. A certain GAP and a certain G protein happen to be expressed in the same time and place, and that is how the cell ensures specificity. Meanwhile, scaffold proteins can also sequester the proper GAP to its G protein and enhance the proper binding interactions. These binding interactions may be specific for a particular GAP and G protein. Also, GAPs may have particular amino acid domains that recognize only a particular G protein. Binding to other G proteins may not have the same favorable interactions, and they therefore do not interact. GAPs can, therefore, regulate specific G proteins. Examples and classification EIF5 is a GTPase-activating protein. Furthermore, YopE is a protein domain that is a Rho GTPase-activating protein (GAP), which targets small GTPases such as RhoA, Rac1, and Rac2. Monomeric The GAPs that act on small GTP-binding proteins of the Ras superfamily have conserved structures and use similar mechanisms, An example of a GTPase is the monomer Ran, which is found in the cytosol as well as the nucleus. Hydrolysis of GTP by Ran is thought to provide the energy needed to transport nuclear proteins into the cell. Ran is turned on and off by GEFs and GAPs, respectively. Heterotrimeric Most GAPs that act on alpha subunits of heterotrimeric G