Crystal structures of Candida albicans phosphodiesterase-2 and implication on its biological functions
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 th...
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Published in | Biochemistry (Easton) Vol. 57; no. 42; pp. 6070 - 6077 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
04.10.2018
|
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Present address: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/acs.biochem.8b00707 |