Crystal Structures of Candida albicans Phosphodiesterase 2 and Implications for Its Biological Functions
[5]
- Beijing Technology and Business Univ. (China)
- Univ. of North Carolina, Chapel Hill, NC (United States); Sun Yat-Sen Univ., Guangzhou (China)
- Univ. of North Carolina, Chapel Hill, NC (United States); Univ. of Electronic Science and Technology of China, Sichuan (China)
- National Inst. of Health, Research Triangle Park, NC (United States)
- Univ. of North Carolina, Chapel Hill, NC (United States)
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 KM of 35 nM. It does not effectively hydrolyze cGMP as shown by the 1.32 × 105-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. In conclusion, this feature of caPDE2 may provide a structural basis for the design of selective inhibitors for the treatment of yeast infection.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Inst. of Health; National Natural Science Foundation of China; National Inst. of Environmental Health Sciences
- OSTI ID:
- 1482251
- Journal Information:
- Biochemistry, Journal Name: Biochemistry Journal Issue: 42 Vol. 57; ISSN 0006-2960
- Publisher:
- American Chemical Society (ACS)Copyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
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