1MKD

crystal structure of PDE4D catalytic domain and zardaverine complex

Summary for 1MKD

• Entry DOI: 10.2210/pdb1mkd/pdb
• Descriptor: Phosphodiesterase 4D, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: pde, zardaverine, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q08499
• Total number of polymer chains: 12
• Total formula weight: 457099.84

Authors

Lee, M.E.,Markowitz, J.,Lee, J.-O.,Lee, H. (deposition date: 2002-08-29, release date: 2003-03-01, Last modification date: 2024-03-13)

Primary citation

Lee, M.E.,Markowitz, J.,Lee, J.-O.,Lee, H.
Crystal structure of phosphodiesterase 4D and inhibitor complex
FEBS LETT., 530:53-58, 2002

PubMed Abstract: 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.

PubMed: 12387865
DOI: 10.1016/S0014-5793(02)03396-3

Experimental method

X-RAY DIFFRACTION (2.9 Å)