机构：[1]Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China[2]Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina 27599-7260, United States[3]Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, Research Triangle Park, North Carolina 27709, United States[4]Individualized Medication Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China 610072四川省人民医院[5]School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China.
The cAMP signaling system plays important roles in the physiological processes of pathogen yeast Candida albicans, but its functional mechanism has not been well illustrated. Here, we report the enzymatic characterization and crystal structures of C. albicans phosphodiesterase 2 (caPDE2) in the unliganded and 3-isobutyl-1-methylxanthine-complexed forms. caPDE2 is a monomer in liquid and crystal states and specifically hydrolyzes cAMP with a K-M of 35 nM. It does not effectively hydrolyze cGMP as shown by the 1.32 X 10(5)-fold specificity of cAMP/cGMP. The crystal structure of caPDE2 shows significant differences from those of human PDEs. First, the N-terminal fragment of caPDE2 (residues 1-201) tightly associates with the catalytic domain to form a rigid molecular entity, implying its stable molecular conformation for C. albicans to resist environmental stresses. Second, the M-loop, a critical fragment for binding of the substrate and inhibitors to human PDEs, is not a part of the caPDE2 active site. This feature of caPDE2 may provide a structural basis for the design of selective inhibitors for the treatment of yeast infection.
基金：
National Institutes of
Health Grant GM59791 to H.K., the National Natural Science
Foundation of China (31471626 and 31291944, Y.W.), and
the Intramural Research Program of the National Institute of
Environmental Health Sciences (H.W.).
第一作者机构：[1]Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
共同第一作者：
通讯作者：
通讯机构：[2]Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina 27599-7260, United States[4]Individualized Medication Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China 610072
推荐引用方式(GB/T 7714)：
Yao Ting,Huang Yiyou,Zhang Meng,et al.Crystal Structures of Candida albicans Phosphodiesterase 2 and Implications for Its Biological Functions[J].BIOCHEMISTRY.2018,57(42):6070-6077.doi:10.1021/acs.biochem.8b00707.
APA：
Yao, Ting,Huang, Yiyou,Zhang, Meng,Chen, Yujuan,Pei, Hairun...&Ke, Hengming.(2018).Crystal Structures of Candida albicans Phosphodiesterase 2 and Implications for Its Biological Functions.BIOCHEMISTRY,57,(42)
MLA：
Yao, Ting,et al."Crystal Structures of Candida albicans Phosphodiesterase 2 and Implications for Its Biological Functions".BIOCHEMISTRY 57..42(2018):6070-6077
