4iam: Difference between revisions
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== | ==Crystal Structure of the C139A mutant of nostoc H-NOX domain== | ||
[[4iam]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAM OCA]. | <StructureSection load='4iam' size='340' side='right'caption='[[4iam]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4iam]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nostoc_sp._PCC_7120_=_FACHB-418 Nostoc sp. PCC 7120 = FACHB-418]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IAM FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=4iam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iam OCA], [https://pdbe.org/4iam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iam RCSB], [https://www.ebi.ac.uk/pdbsum/4iam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iam ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8YUQ7_NOSS1 Q8YUQ7_NOSS1] | |||
<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. | |||
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> | |||
<ref | |||
[[Category: | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
[[Category: | </div> | ||
[[Category: Kumar | <div class="pdbe-citations 4iam" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Nostoc sp. PCC 7120 = FACHB-418]] | |||
[[Category: Kumar V]] | |||
[[Category: Van den Akker F]] | |||
Latest revision as of 18:18, 20 September 2023
Crystal Structure of the C139A mutant of nostoc H-NOX domainCrystal Structure of the C139A mutant of nostoc H-NOX domain
Structural highlights
FunctionPublication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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