1mkd | pdb_00001mkd
crystal structure of PDE4D catalytic domain and zardaverine complex
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| 1mkd, resolution 2.90Å | |||||||||||||
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| Ligands: | MG, ZAR, ZN | ||||||||||||
| Activity: | 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
Cyclic nucleotide phosphodiesterases (PDEs) regulate physiological processes by degrading intracellular second messengers, adenosine-3',5'-cyclic phosphate or guanosine-3',5'-cyclic phosphate. The first crystal structure of PDE4D catalytic domain and a bound inhibitor, zardaverine, was determined. Zardaverine binds to a highly conserved pocket that includes the catalytic metal binding site. Zardaverine fills only a portion of the active site pocket. More selective PDE4 inhibitors including rolipram, cilomilast and roflumilast have additional functional groups that can utilize the remaining empty space for increased binding energy and selectivity. In the crystal structure, the catalytic domain of PDE4D possesses an extensive dimerization interface containing residues that are highly conserved in PDE1, 3, 4, 8 and 9. Mutations of R358D or D322R among these interface residues prohibit dimerization of the PDE4D catalytic domain in solution.
About this Structure
1MKD is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of phosphodiesterase 4D and inhibitor complex(1)., Lee ME, Markowitz J, Lee JO, Lee H, FEBS Lett. 2002 Oct 23;530(1-3):53-8. PMID:12387865
Page seeded by OCA on Sun Mar 30 22:17:11 2008
