A major thrust area in my laboratory is to understand how GTPases hydrolyze GTP ? We identified an atypical subgroup of GTPases termed the HAS-GTPases or ‘Hydrophobic Amino acid Substituted-GTPases’ (Mishra, et.al. Proteins, 2005). HAS-GTPases are atypical and interesting for the following reasons. These hydrolyze GTP despite lacking a catalytic glutamine, which is conserved and important to the function of most GTPases. Yet, HAS-GTPases hydrolyze GTP efficiently. A puzzle, however, is that in classical GTPases like Ras, an analogous mutation of a glutamine to a hydrophobic residue renders it oncogenic. We suggested novel catalytic mechanisms for HAS-GTPases (Mishra et.al. Proteins, 2005) and indeed, diverse novel mechanisms discovered later, concur with our predictions. Subsequently, we showed that a number of HAS-GTPases bind ribosomal subunits and likely participate in its biogenesis, however the catalytic mechanisms adopted by them continue to fascinate us. My talk will address variations in GTP hydrolysis mechanisms and present a theory we propose to that unifies these variations. Interestingly, we decipher how structural plasticity allows two distinct GTP hydrolysis mechanisms to operate in the same GTPase depending on the biological context it has to satisfy.