1tbb: Difference between revisions

Revision as of 09:45, 3 May 2008

Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Rolipram

OverviewOverview

Phosphodiesterases (PDEs) comprise a family of enzymes that modulate the immune response, inflammation, and memory, among many other functions. There are three types of PDEs: cAMP-specific, cGMP-specific, and dual-specific. Here we describe the mechanism of nucleotide selectivity on the basis of high-resolution co-crystal structures of the cAMP-specific PDE4B and PDE4D with AMP, the cGMP-specific PDE5A with GMP, and the apo-structure of the dual-specific PDE1B. These structures show that an invariant glutamine functions as the key specificity determinant by a "glutamine switch" mechanism for recognizing the purine moiety in cAMP or cGMP. The surrounding residues anchor the glutamine residue in different orientations for cAMP and for cGMP. The PDE1B structure shows that in dual-specific PDEs a key histidine residue may enable the invariant glutamine to toggle between cAMP and cGMP. The structural understanding of nucleotide binding enables the design of new PDE inhibitors that may treat diseases in which cyclic nucleotides play a critical role.

About this StructureAbout this Structure

1TBB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases., Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G, Mol Cell. 2004 Jul 23;15(2):279-86. PMID:15260978 Page seeded by OCA on Sat May 3 09:45:34 2008

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OCA

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 [[Image:1tbb.gif|left|200px]]
- {{Structure
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </span>
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-|GENE= PDE4D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1tbb|  PDB=1tbb  |  SCENE=  }}
-|RELATEDENTRY=[[1t9r|1T9R]], [[1t9s|1T9S]], [[1taz|1TAZ]], [[1tb5|1TB5]], [[1tb7|1TB7]], [[1tbf|1TBF]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tbb OCA], [http://www.ebi.ac.uk/pdbsum/1tbb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tbb RCSB]</span>
-}}
 '''Catalytic Domain Of Human Phosphodiesterase 4D In Complex With Rolipram'''
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 [[Category: Zhang, C.]]
 [[Category: Zhang, K Y.J.]]
-[[Category: pde4d]]
+[[Category: Pde4d]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 09:45:34 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:53:47 2008''