Structural insight into substrate specificity of phosphodiesterase 10.

Structural insight into substrate specificity of phosphodiesterase 10. Research Abstract Details 

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Structural insight into substrate specificity of phosphodiesterase 10. Abstract Text:

Huanchen Wang,Yudong Liu,Jing Hou,Meiyan Zheng,Howard Robinson,Hengming Ke,

Phosphodiesterases (PDEs) hydrolyze the second messengers cAMP and cGMP. It remains unknown how individual PDE families selectively recognize cAMP and cGMP. This work reports structural studies on substrate specificity. The crystal structures of the catalytic domains of the D674A and D564N mutants of PDE10A2 in complex with cAMP and cGMP reveal that two substrates bind to the active site with the same syn configuration but different orientations and interactions. The products AMP and GMP bind PDE10A2 with the anti configuration and interact with both divalent metals, in contrast to no direct contact of the substrates. The structures suggest that the syn configurations of cAMP and cGMP are the genuine substrates for PDE10 and the specificity is achieved through the different interactions and conformations of the substrates. The PDE10A2 structures also show that the conformation of the invariant glutamine is locked by two hydrogen bonds and is unlikely to switch for substrate recognition. Sequence alignment shows a potential pocket, in which variation of amino acids across PDE families defines the size and shape of the pocket and thus determines the substrate specificity.

Structural insight into substrate specificity of phosphodiesterase 10. Publishing Authors By Initials

H Wang,Y Liu,J Hou,M Zheng,H Robinson,H Ke,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

PUBMED ID PMID:

MEDLINE DATE:

Structural insight into substrate specificity of phosphodiesterase 10. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 5782-7

Journal Abbreviation:

ISSN: 0027-8424

DAY: 26

MONTH: 03

YEAR: 2007

Structural insight into substrate specificity of phosphodiesterase 10. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Structural insight into substrate specificity of phosphodiesterase 10. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: metabolism

Chemical & Substance for Abstract: Structural insight into substrate specificity of phosphodiesterase 10. Information

Substance Name: Phosphoric Diester Hydrolases

Registry Number: EC 3.1.4.-

Grant and Affiliation Information for Structural insight into substrate specificity of phosphodiesterase 10.

AFFILIATION: Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7260, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM59791

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

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