4iah

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_4iah| PDB=4iah | SCENE= }}
+
==Crystal Structure of BAY 60-2770 bound C139A H-NOX domain with S-nitrosylated conserved C122==
-
===Crystal Structure of BAY 60-2770 bound C139A H-NOX domain with S-nitrosylated conserved C122===
+
<StructureSection load='4iah' size='340' side='right' caption='[[4iah]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_23614626}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4iah]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Anabaena_7120 Anabaena 7120]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IAH FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1DX:4-({(4-CARBOXYBUTYL)[2-(5-FLUORO-2-{[4-(TRIFLUOROMETHYL)BIPHENYL-4-YL]METHOXY}PHENYL)ETHYL]AMINO}METHYL)BENZOIC+ACID'>1DX</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
 +
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene></td></tr>
 +
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l6j|3l6j]], [[2o09|2o09]], [[2o0c|2o0c]], [[2o0g|2o0g]], [[4iae|4iae]], [[4iam|4iam]]</td></tr>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alr2278 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=103690 Anabaena 7120])</td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Guanylate_cyclase Guanylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.2 4.6.1.2] </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=4iah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iah OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iah RCSB], [http://www.ebi.ac.uk/pdbsum/4iah PDBsum]</span></td></tr>
 +
</table>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The soluble guanylyl cyclase (sGC) is an important receptor for nitric oxide (NO). Nitric oxide activates sGC several hundred fold to generate cGMP from GTP. Because of sGC's salutary roles in cardiovascular physiology, it has received substantial attention as a drug target. The heme domain of sGC is key to its regulation as it not only contains the NO activation site but also harbors sites for NO-independent sGC activators as well an S-nitrosylation site (beta1 C122) involved in desensitization. Here we report the crystal structure of the activator BAY 60-2770 bound to the Nostoc H-NOX domain that is homologous to sGC. The structure reveals that BAY 60-2770 has displaced the heme and acts as a heme mimetic via carboxylate-mediated interactions with the conserved YxSxR motif as well as hydrophobic interactions. Comparisons with the previously determined BAY 58-2667 bound structure reveal that BAY 60-2770 is more ordered in its hydrophobic tail region. sGC activity assays demonstrate that BAY 60-2770 has about 10% higher fold maximal stimulation compared to BAY 58-2667. S-Nitrosylation of the BAY 60-2770 substituted Nostoc H-NOX domain causes subtle changes in the vicinity of the S-nitrosylated C122 residue. These shifts could impact the adjacent YxSxR motif and alphaF helix and as such potentially inhibit either heme incorporation or NO-activation of sGC and thus provide a structural basis for desensitization.
-
==About this Structure==
+
Insights into BAY 60-2770 Activation and S-Nitrosylation-Dependent Desensitization of Soluble Guanylyl Cyclase via Crystal Structures of Homologous Nostoc H-NOX Domain Complexes.,Kumar V, Martin F, Hahn MG, Schaefer M, Stamler JS, Stasch JP, van den Akker F Biochemistry. 2013 May 7. PMID:23614626<ref>PMID:23614626</ref>
-
[[4iah]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Anabaena_7120 Anabaena 7120]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAH OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<ref group="xtra">PMID:023614626</ref><references group="xtra"/><references/>
+
</div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Anabaena 7120]]
[[Category: Anabaena 7120]]
[[Category: Guanylate cyclase]]
[[Category: Guanylate cyclase]]
-
[[Category: Akker, F van den.]]
+
[[Category: Akker, F van den]]
-
[[Category: Kumar, V.]]
+
[[Category: Kumar, V]]
[[Category: Bay 60-2770]]
[[Category: Bay 60-2770]]
[[Category: Conserved c122]]
[[Category: Conserved c122]]

Revision as of 12:57, 5 January 2015

Crystal Structure of BAY 60-2770 bound C139A H-NOX domain with S-nitrosylated conserved C122

4iah, resolution 2.80Å

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/4iah"
Personal tools