Crystal structures of Candida albicans phosphodiesterase-2 and implication on its biological functions

• Published in: Biochemistry (Easton) Vol. 57; no. 42; pp. 6070 - 6077
• Main Authors: Yao, Ting, Huang, Yiyou, Zhang, Meng, Chen, Yujuan, Pei, Hairun, Shi, Jianyou, Wang, Huanchen, Wang, Yousheng, Ke, Hengming
• Format: Journal Article
• Language: English
• Published: 04.10.2018
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/acs.biochem.8b00707

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 Candida albicans phosphodiesterase 2 (caPDE2) in the unliganded and IBMX complexed forms. CaPDE2 is a monomer in liquid and crystal states and specifically hydrolyzes cAMP with K M of 35 nM. It does not effectively hydrolyze cGMP as shown by 1.32×10 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 Candida albicans to resist environmental stresses. Second, the M-loop, a critical fragment for binding of substrate and inhibitors to human PDEs, is not a part of the caPDE2 active site. This feature of caPDE2 may provide structure basis for design of selective inhibitors for treatment of yeast infection. Dramatic conformation difference between the M-loops of yeast caPDE2 and PDE4D.