1mkd
From Proteopedia
(New page: 200px<br /> <applet load="1mkd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mkd, resolution 2.90Å" /> '''crystal structure o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1mkd.gif|left|200px]]<br /> | + | [[Image:1mkd.gif|left|200px]]<br /><applet load="1mkd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mkd" size=" | + | |
caption="1mkd, resolution 2.90Å" /> | caption="1mkd, resolution 2.90Å" /> | ||
'''crystal structure of PDE4D catalytic domain and zardaverine complex'''<br /> | '''crystal structure of PDE4D catalytic domain and zardaverine complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cyclic nucleotide phosphodiesterases (PDEs) regulate physiological | + | 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. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1MKD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, MG and ZAR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1MKD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ZAR:'>ZAR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MKD OCA]. |
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Lee, H.]] | [[Category: Lee, H.]] | ||
| - | [[Category: Lee, J | + | [[Category: Lee, J O.]] |
| - | [[Category: Lee, M | + | [[Category: Lee, M E.]] |
[[Category: Markowitz, J.]] | [[Category: Markowitz, J.]] | ||
[[Category: MG]] | [[Category: MG]] | ||
| Line 28: | Line 27: | ||
[[Category: zardaverine]] | [[Category: zardaverine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:56:03 2008'' |
Revision as of 11:56, 21 February 2008
|
crystal structure of PDE4D catalytic domain and zardaverine complex
Contents |
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.
Disease
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[600129]
About this Structure
1MKD is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as 3',5'-cyclic-nucleotide phosphodiesterase, with EC number 3.1.4.17 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 Thu Feb 21 13:56:03 2008
Categories: 3',5'-cyclic-nucleotide phosphodiesterase | Homo sapiens | Single protein | Lee, H. | Lee, J O. | Lee, M E. | Markowitz, J. | MG | ZAR | ZN | Pde | Zardaverine
