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Title: Dual specificity and novel structural folding of yeast phosphodiesterase-1 for hydrolysis of second messengers cyclic adenosine and guanosine 3',5'-Monophosphate

Cyclic nucleotide phosphodiesterases (PDEs) decompose second messengers cAMP and cGMP that play critical roles in many physiological processes. PDE1 of Saccharomyces cerevisiae has been subcloned and expressed in Escherichia coli. Recombinant yPDE1 has a KM of 110 μM and a kcat of 16.9 s⁻¹ for cAMP and a KM of 105 μM and a kcat of 11.8 s₅⁻¹ for cGMP. Thus, the specificity constant (kcat/KMcAMP)/(kcat/KMcGMP) of 1.4 indicates a dual specificity of yPDE1 for hydrolysis of both cAMP and cGMP. The crystal structures of unliganded yPDE1 and its complex with GMP at 1.31 Å resolution reveal a new structural folding that is different from those of human PDEs but is partially similar to that of some other metalloenzymes such as metallo-β-lactamase. In spite of their different structures and divalent metals, yPDE1 and human PDEs may share a common mechanism for hydrolysis of cAMP and cGMP.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [2]
  1. Beijing Technology and Business Univ., Beijing (China); Univ. of North Carolina, Chapel Hill, NC (United States)
  2. Univ. of North Carolina, Chapel Hill, NC (United States)
  3. Univ. of North Carolina, Chapel Hill, NC (United States); Sun Yat-Sen Univ., Guangzhou (China)
  4. Brookhaven National Lab. (BNL), Upton, NY (United States)
  5. Sun Yat-Sen Univ., Guangzhou (China)
  6. Beijing Technology and Business Univ., Beijing (China)
Publication Date:
OSTI Identifier:
1179586
Type:
Published Article
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 53; Journal Issue: 30; Related Information: CHORUS Timestamp: 2016-09-01 11:19:24; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES