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


RESULTS
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.


CONCLUSIONS
This structure provides a new template for target-based pharmaceutical design against RhoA.
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People's Republic of China.
Zhaowei
Z
Yan
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People's Republic of China.
Sheng
S
Ma
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People's Republic of China.
Yan
Y
Zhang
Wuxi Biortus Biosciences Co.Ltd, Jiangyin, Jiangsu, 214437, People's Republic of China.
La
Ma
Wuxi Biortus Biosciences Co.Ltd, Jiangyin, Jiangsu, 214437, People's Republic of China.
Feng
F
Wang
Shanghai Key Laboratory of New Drug Design, School of Pharmacy East China University of Science and Technology, Shanghai, 200237, People's Republic of China. jianli@ecust.edu.cn.
Jian
J
Li
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People's Republic of China. miaolysuzhou@163.com.
Liyan
L
Miao
D003460:Crystallization; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism
D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate; D020742:rhoA GTP-Binding Protein
RhoA-PDZRhoGEF-inhibitor HL47 ternary complex; Target-based pharmaceutical design; X-ray structure