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3ITM

Catalytic domain of hPDE2A

Summary for 3ITM
Entry DOI10.2210/pdb3itm/pdb
Related1Z1L
DescriptorcGMP-dependent 3',5'-cyclic phosphodiesterase, ZINC ION (3 entities in total)
Functional Keywordszn-binding, all-alpha helical, cgmp, hydrolase, membrane
Biological sourceHomo sapiens (human)
Cellular locationMembrane; Peripheral membrane protein (Potential): O00408
Total number of polymer chains4
Total formula weight161162.04
Authors
Pandit, J. (deposition date: 2009-08-28, release date: 2009-10-27, Last modification date: 2024-02-21)
Primary citationPandit, J.,Forman, M.D.,Fennell, K.F.,Dillman, K.S.,Menniti, F.S.
Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct.
Proc.Natl.Acad.Sci.USA, 106:18225-18230, 2009
Cited by
PubMed Abstract: We report the X-ray crystal structure of a phosphodiesterase (PDE) that includes both catalytic and regulatory domains. PDE2A (215-900) crystallized as a dimer in which each subunit had an extended organization of regulatory GAF-A and GAF-B and catalytic domains connected by long alpha-helices. The subunits cross at the GAF-B/catalytic domain linker, and each side of the dimer contains in series the GAF-A and GAF-B of one subunit and the catalytic domain of the other subunit. A dimer interface extends over the entire length of the molecule. The substrate binding pocket of each catalytic domain is occluded by the H-loop. We deduced from comparisons with structures of isolated, ligand-bound catalytic subunits that the H-loop swings out to allow substrate access. However, in dimeric PDE2A (215-900), the H-loops of the two catalytic subunits pack against each other at the dimer interface, necessitating movement of the catalytic subunits to allow for H-loop movement. Comparison of the unliganded GAF-B of PDE2A (215-900) with previous structures of isolated, cGMP-bound GAF domains indicates that cGMP binding induces a significant shift in the GAF-B/catalytic domain linker. We propose that cGMP binding to GAF-B causes movement, through this linker region, of the catalytic domains, such that the H-loops no longer pack at the dimer interface and are, instead, free to swing out to allow substrate access. This increase in substrate access is proposed as the basis for PDE2A activation by cGMP and may be a general mechanism for regulation of all PDEs.
PubMed: 19828435
DOI: 10.1073/pnas.0907635106
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.49 Å)
Structure validation

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