3jwr

From Proteopedia

(Difference between revisions)

Revision as of 08:05, 6 September 2023

Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.

Structural highlights

3jwr is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.994Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PDE6C_HUMAN Progressive cone dystrophy;Achromatopsia. The disease is caused by mutations affecting the gene represented in this entry.

Function

PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.PDE6C_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The inhibitory interaction of phosphodiesterase-6 (PDE6) with its gamma-subunit (Pgamma) is pivotal in vertebrate phototransduction. Here, crystal structures of a chimaeric PDE5/PDE6 catalytic domain (PDE5/6cd) complexed with sildenafil or 3-isobutyl-1-methylxanthine and the Pgamma-inhibitory peptide Pgamma(70-87) have been determined at 2.9 and 3.0 A, respectively. These structures show the determinants and the mechanism of the PDE6 inhibition by Pgamma and suggest the conformational change of Pgamma on transducin activation. Two variable H- and M-loops of PDE5/6cd form a distinct interface that contributes to the Pgamma-binding site. This allows the Pgamma C-terminus to fit into the opening of the catalytic pocket, blocking cGMP access to the active site. Our analysis suggests that disruption of the H-M loop interface and Pgamma-binding site is a molecular cause of retinal degeneration in atrd3 mice. Comparison of the two PDE5/6cd structures shows an overlap between the sildenafil and Pgamma(70-87)-binding sites, thereby providing critical insights into the side effects of PDE5 inhibitors on vision.

Structural basis of phosphodiesterase 6 inhibition by the C-terminal region of the gamma-subunit.,Barren B, Gakhar L, Muradov H, Boyd KK, Ramaswamy S, Artemyev NO EMBO J. 2009 Nov 18;28(22):3613-22. Epub 2009 Oct 1. PMID:19798052^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Barren B, Gakhar L, Muradov H, Boyd KK, Ramaswamy S, Artemyev NO. Structural basis of phosphodiesterase 6 inhibition by the C-terminal region of the gamma-subunit. EMBO J. 2009 Nov 18;28(22):3613-22. Epub 2009 Oct 1. PMID:19798052 doi:10.1038/emboj.2009.284

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3jwr"

@@ Line 3: / Line 3: @@
 <StructureSection load='3jwr' size='340' side='right'caption='[[3jwr]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3jwr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JWR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JWR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3jwr]] is a 4 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=3JWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JWR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IBM:3-ISOBUTYL-1-METHYLXANTHINE'>IBM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.994&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jwq|3jwq]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IBM:3-ISOBUTYL-1-METHYLXANTHINE'>IBM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-GMP_phosphodiesterase 3',5'-cyclic-GMP phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.35 3.1.4.35] </span></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=3jwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwr OCA], [https://pdbe.org/3jwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jwr RCSB], [https://www.ebi.ac.uk/pdbsum/3jwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jwr ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwr OCA], [http://pdbe.org/3jwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jwr RCSB], [http://www.ebi.ac.uk/pdbsum/3jwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jwr ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CNRG_HUMAN CNRG_HUMAN]] Defects in PDE6G are the cause of retinitis pigmentosa type 57 (RP57) [MIM:[http://omim.org/entry/613582 613582]]. RP57 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:20655036</ref>
+[https://www.uniprot.org/uniprot/PDE6C_HUMAN PDE6C_HUMAN] Progressive cone dystrophy;Achromatopsia. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/PDE5A_HUMAN PDE5A_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. [[http://www.uniprot.org/uniprot/CNRG_HUMAN CNRG_HUMAN]] Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
+[https://www.uniprot.org/uniprot/PDE5A_HUMAN PDE5A_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.[https://www.uniprot.org/uniprot/PDE6C_HUMAN PDE6C_HUMAN]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 33: @@
 ==See Also==
-*[[Phosphodiesterase|Phosphodiesterase]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: 3',5'-cyclic-GMP phosphodiesterase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Artemyev, N O]]
+[[Category: Artemyev NO]]
-[[Category: Barren, B]]
+[[Category: Barren B]]
-[[Category: Boyd, K K]]
+[[Category: Boyd KK]]
-[[Category: Gakhar, L]]
+[[Category: Gakhar L]]
-[[Category: Muradov, H]]
+[[Category: Muradov H]]
-[[Category: Ramaswamy, S]]
+[[Category: Ramaswamy S]]
-[[Category: Cgmp]]
-[[Category: Hydrolase]]
-[[Category: Mostly alpha]]
-[[Category: Polymorphism]]
-[[Category: Sensory transduction]]
-[[Category: Vision]]

3jwr

From Proteopedia

Revision as of 08:05, 6 September 2023

Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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