GTPase Catalysis by Ras and Other G-proteins: Insights from Substrate Directed SuperImposition

Comparisons of different protein structures are commonly carried out by superimposing the coordinates of the protein backbones or selected parts of the proteins. When the objective is analysis of similarities and differences in the enzymeʹs active site, there is an inherent problem in using the same domains for the superimposition. In this work we use a comparative approach termed here “Substrate Directed SuperImposition” (SDSI). It entails the superimposition of multiple protein–substrate structures using exclusively the coordinates of the comparable substrates. SDSI has the advantage of unbiased comparison of the active-site environment from the substrateʹs point of view. Our analysis extends previous usage of similar approaches to comparison of enzyme catalytic machineries.