7mri: Difference between revisions
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==Crystal structure of N63T yeast iso-1-cytochrome c== | ==Crystal structure of N63T yeast iso-1-cytochrome c== | ||
<StructureSection load='7mri' size='340' side='right'caption='[[7mri]]' scene=''> | <StructureSection load='7mri' size='340' side='right'caption='[[7mri]], [[Resolution|resolution]] 2.46Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MRI FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MRI FirstGlance]. <br> | ||
</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=7mri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mri OCA], [https://pdbe.org/7mri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mri RCSB], [https://www.ebi.ac.uk/pdbsum/7mri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mri ProSAT]</span></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]] 2.46Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</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=7mri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mri OCA], [https://pdbe.org/7mri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mri RCSB], [https://www.ebi.ac.uk/pdbsum/7mri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mri ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Naturally-occurring variants of human cytochrome c (Cytc) that induce thrombocytopenia IV occur within Omega-loop C (residues 40-57). These variants enhance the peroxidase activity of human Cytc apparently by facilitating access to the heme by destabilizing Omega-loops C and D (residues 70-85). Given the importance of peroxidase activity in the early stages of apoptosis, we identified three sites with the EVmutation algorithm in or near Omega-loop C that coevolve and differ between yeast iso-1-Cytc and human Cytc. We prepared iso-1-Cytc variants with all possible combinations of the S40T, V57I and N63T substitutions to determine if these residues decrease the peroxidase activity of iso-1-Cytc to that of human Cytc producing an effective off state for a peroxidase signaling switch. At pH 6 and above, all variants significantly decreased peroxidase activity. However, the correlation of peroxidase activity with local and global stability, expected if cooperative unfolding of Omega-loops C and D is required for peroxidase activity, was generally poor. The m-values derived from the guanidine hydrochloride dependence of the kinetics of imidazole binding to horse Cytc, which is well-characterized by native-state hydrogen exchange methods, and K72A/K73A/K79A iso-1-Cytc show that local structural fluctuations and not subglobal cooperative unfolding of Omega-loops C and D are sufficient to permit binding of a small molecule like peroxide to the heme. A 2.46 A structure of N63T iso-1-Cytc identifies a change to a hydrogen bond network linking Omega-loops C and D that could modulate the local fluctuations needed for the intrinsic peroxidase activity of Cytc. | |||
Effect on intrinsic peroxidase activity of substituting coevolved residues from Omega-loop C of human cytochrome c into yeast iso-1-cytochrome c.,Frederick AK, Thompson SL, Vakharia ZM, Cherney MM, Lei H, Evenson G, Bowler BE J Inorg Biochem. 2022 Jul;232:111819. doi: 10.1016/j.jinorgbio.2022.111819. Epub , 2022 Apr 6. PMID:35428021<ref>PMID:35428021</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7mri" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cytochrome C 3D structures|Cytochrome C 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
