The structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47.

Abstract

To study the structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47, and to provide an easier template for R&D of RhoA inhibitor. Our initial attempts to obtain a binary complex of RhoA with the inhibitor HL47 were unsuccessful probably due to the presence of GDP. By targeting a ternary complex involving the RhoA-specific guanine nucleotide exchange factor PDZRhoGEF, we eliminated GDP and obtained a 2.3Å structure of the RhoA-PDZRhoGEF-inhibitor HL47 ternary complex. This structure provides a new template for target-based pharmaceutical design against RhoA.