1OIX | pdb_00001oix

Crystallographic Evidence for Substrate-Assisted GTP Hydrolysis by a Small GTP Binding Protein

(2005) Structure 13: 533

• PubMed: 15837192 Search on PubMed
• DOI: https://doi.org/10.1016/j.str.2005.01.014
• Primary Citation of Related Structures:  
  1OIX


• PubMed Abstract: 
  

  GTP hydrolysis by small GTP binding proteins of the Ras superfamily is a universal reaction that controls multiple cellular regulations. Its enzymic mechanism has been the subject of long-standing debates as to the existence/identity of the general base and the electronic nature of its transition state. Here we report the high-resolution crystal structure of a small GTP binding protein, Rab11, solved in complex with GDP and Pi. Unexpectedly, a Pi oxygen and the GDP-cleaved oxygen are located less than 2.5 A apart, suggesting that they share a proton, likely in the form of a low-barrier hydrogen bond. This implies that the gamma-phosphate of GTP was protonated; hence, that GTP acts as a general base. Furthermore, this interaction should establish at, and stabilize, the transition state. Altogether, we propose a revised model for the GTPase reaction that should reconcile earlier models into a unique substrate-assisted mechanism.

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Organizational Affiliation: 

Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.