1mkd

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:26, 13 March 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1mkd.gif|left|200px]]
 
-
{{Structure
+
==crystal structure of PDE4D catalytic domain and zardaverine complex==
-
|PDB= 1mkd |SIZE=350|CAPTION= <scene name='initialview01'>1mkd</scene>, resolution 2.90&Aring;
+
<StructureSection load='1mkd' size='340' side='right'caption='[[1mkd]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=ZAR:6-(4-DIFLUOROMETHOXY-3-METHOXY-PHENYL)-2H-PYRIDAZIN-3-ONE'>ZAR</scene>
+
<table><tr><td colspan='2'>[[1mkd]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MKD FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
-
|GENE=
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZAR:6-(4-DIFLUOROMETHOXY-3-METHOXY-PHENYL)-2H-PYRIDAZIN-3-ONE'>ZAR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-
}}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mkd OCA], [https://pdbe.org/1mkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mkd RCSB], [https://www.ebi.ac.uk/pdbsum/1mkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mkd ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:[https://omim.org/entry/614613 614613]. ACRDYS2 is a pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.<ref>PMID:22464250</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mk/1mkd_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mkd ConSurf].
 +
<div style="clear:both"></div>
-
'''crystal structure of PDE4D catalytic domain and zardaverine complex'''
+
==See Also==
-
 
+
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-
 
+
== References ==
-
==Overview==
+
<references/>
-
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.
+
__TOC__
-
 
+
</StructureSection>
-
==Disease==
+
-
Known disease associated with this structure: Stroke, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600129 600129]]
+
-
 
+
-
==About this Structure==
+
-
1MKD is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MKD 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:[http://www.ncbi.nlm.nih.gov/pubmed/12387865 12387865]
+
-
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Lee, H.]]
+
[[Category: Lee H]]
-
[[Category: Lee, J O.]]
+
[[Category: Lee J-O]]
-
[[Category: Lee, M E.]]
+
[[Category: Lee ME]]
-
[[Category: Markowitz, J.]]
+
[[Category: Markowitz J]]
-
[[Category: MG]]
+
-
[[Category: ZAR]]
+
-
[[Category: ZN]]
+
-
[[Category: pde]]
+
-
[[Category: zardaverine]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:44:30 2008''
+

Current revision

crystal structure of PDE4D catalytic domain and zardaverine complex

PDB ID 1mkd

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mkd"
Personal tools