2hd1

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{{STRUCTURE_2hd1| PDB=2hd1 | SCENE= }}
{{STRUCTURE_2hd1| PDB=2hd1 | SCENE= }}
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'''Crystal structure of PDE9 in complex with IBMX'''
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===Crystal structure of PDE9 in complex with IBMX===
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==Overview==
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Cyclic nucleotide phosphodiesterases (PDEs) are enzymes controlling cellular concentrations of the second messengers cAMP and cGMP. The crystal structure of the catalytic domain of PDE9A2, a member of a PDE family specifically hydrolyzing cGMP, has been determined at 2.23-A resolution. The PDE9A2 catalytic domain closely resembles the cAMP-specific PDE4D2 but is significantly different from the cGMP-specific PDE5A1, implying that each individual PDE family has its own characteristic substrate recognition mechanism. The different conformations of the H and M loops between PDE9A2 and PDE5A1 imply their less critical roles in nucleotide recognition. The nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) binds to a similar subpocket in the active sites of PDE4, PDE5, and PDE9 and has a common pattern of the binding. However, significantly different orientations and interactions of IBMXs are observed among the three PDE families and also between two monomers of the PDE9A2 dimer. The kinetic properties of the PDE9A2 catalytic domain similar to those of full-length PDE9A imply that the N-terminal regulatory domain does not significantly alter the catalytic activity and the IBMX inhibition.
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{{ABSTRACT_PUBMED_15210993}}
==Disease==
==Disease==
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[[Category: Ibmx]]
[[Category: Ibmx]]
[[Category: Pde9]]
[[Category: Pde9]]
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Revision as of 09:42, 27 July 2008

Image:2hd1.png

Template:STRUCTURE 2hd1

Contents

Crystal structure of PDE9 in complex with IBMX

Template:ABSTRACT PUBMED 15210993

Disease

Known disease associated with this structure: Epilepsy, pyridoxine-dependent OMIM:[107323]

About this Structure

2HD1 is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1tbm. Full crystallographic information is available from OCA.

Reference

Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding., Huai Q, Wang H, Zhang W, Colman RW, Robinson H, Ke H, Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9624-9. Epub 2004 Jun 21. PMID:15210993

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