The structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47
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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 2.3 Å structure of the RhoA-PDZRhoGEF-inhibitor HL47 ternary complex.
This structure provides a new template for target-based pharmaceutical design against RhoA.
KeywordsRhoA-PDZRhoGEF-inhibitor HL47 ternary complex Target-based pharmaceutical design X-ray structure
The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (Grant Nos. 81202394, 21222211, 21372001 and 91313303), the Ministry of Education of China’s Program for New Century Excellent Talents in University (Grant No. NCET-12-0853), the Young Medical Talents Project of Jiangsu Province, and the Applied Basic Research Programs of Suzhou Sci-tech Bureau, China (Grant No. SYS201219).
Supplementary Table 1—Macromolecule production data for RhoA and PDZRhoGEF.
Supplementary Table 2—Crystallization information.
Supplementary Table 3—Data collection and processing.
Supplementary Table 4—Structure refinement.
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