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PDBsum entry 3dys
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References listed in PDB file
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Key reference
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Title
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Structural basis for the catalytic mechanism of human phosphodiesterase 9.
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Authors
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S.Liu,
M.N.Mansour,
K.S.Dillman,
J.R.Perez,
D.E.Danley,
P.A.Aeed,
S.P.Simons,
P.K.Lemotte,
F.S.Menniti.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
13309-13314.
[DOI no: ]
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PubMed id
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Abstract
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The phosphodiesterases (PDEs) are metal ion-dependent enzymes that regulate
cellular signaling by metabolic inactivation of the ubiquitous second messengers
cAMP and cGMP. In this role, the PDEs are involved in many biological and
metabolic processes and are proven targets of successful drugs for the
treatments of a wide range of diseases. However, because of the rapidity of the
hydrolysis reaction, an experimental knowledge of the enzymatic mechanisms of
the PDEs at the atomic level is still lacking. Here, we report the structures of
reaction intermediates accumulated at the reaction steady state in PDE9/crystal
and preserved by freeze-trapping. These structures reveal the catalytic process
of a PDE and explain the substrate specificity of PDE9 in an actual reaction and
the cation requirements of PDEs in general.
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Figure 2.
Stereo diagram of the putative ES complex model illustrates
the recognition of cGMP (magenta carbons) by active PDE9 (green
carbons). Hydrogen bonds are shown by dashed lines.
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Figure 4.
Schematic illustration of the proposed reaction pathway for
PDE9. E, apo enzyme. ES, enzyme/substrate. EP, enzyme/product
complex. E+P, the regenerated enzyme/rebound product complexes.
Dashed lines represent hydrogen/coordination bonds.
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