title: Dual specificity and novel structural folding of yeast phosphodiesterase-1 for hydrolysis of second messengers cyclic adenosine and guanosine 3',5'-monophosphate.
abstract: 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 s(-1) for cGMP. Thus, the specificity constant (kcat/KM(cAMP))/(kcat/KM(cGMP)) 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: Beijing Laboratory for Food Quality and Safety and Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University , Beijing 100048, P. R. China.
authors: Yuanyuan
authors: Y
authors: Tian
authors: Wenjun
authors: W
authors: Cui
authors: Manna
authors: M
authors: Huang
authors: Howard
authors: H
authors: Robinson
authors: Yiqian
authors: Y
authors: Wan
authors: Yousheng
authors: Y
authors: Wang
authors: Hengming
authors: H
authors: Ke
mesh_terms: D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism*; D006152:Cyclic GMP / Q000737:chemistry / Q000378:metabolism*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology*; D013379:Substrate Specificity
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D006152:Cyclic GMP