5i0s: Difference between revisions
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==Thiosulfate bound Cysteine Dioxygenase at pH 6.2== | |||
<StructureSection load='5i0s' size='340' side='right'caption='[[5i0s]], [[Resolution|resolution]] 1.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5i0s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I0S 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]] 1.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=THJ:THIOSULFATE'>THJ</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=5i0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i0s OCA], [https://pdbe.org/5i0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i0s RCSB], [https://www.ebi.ac.uk/pdbsum/5i0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i0s ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CDO1_RAT CDO1_RAT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In mammals, the non-heme iron enzyme cysteine dioxygenase (CDO) helps regulate Cys levels through converting Cys to Cys sulfinic acid. Its activity is in part modulated by the formation of a Cys93-Tyr157 crosslink that increases its catalytic efficiency over 10-fold. Here, 21 high-resolution mammalian CDO structures are used to gain insight into how the Cys-Tyr crosslink promotes activity and how select competitive inhibitors bind. Crystal structures of crosslink-deficient C93A and Y157F variants reveal similar ~1.0-A shifts in the side chain of residue 157, and both variant structures have a new chloride ion coordinating the active site iron. Cys binding is also different from wild-type CDO, and no Cys-persulfenate forms in the C93A or Y157F active sites at pH6.2 or 8.0. We conclude that the crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry. In addition, structures are presented for homocysteine (Hcy), D-Cys, thiosulfate, and azide bound as competitive inhibitors. The observed binding modes of Hcy and D-Cys clarify why they are not substrates, and the binding of azide shows that in contrast to what has been proposed, it does not bind in these crystals as a superoxide mimic. | |||
Structure-Based Insights into the Role of the Cys-Tyr Crosslink and Inhibitor Recognition by Mammalian Cysteine Dioxygenase.,Driggers CM, Kean KM, Hirschberger LL, Cooley RB, Stipanuk MH, Karplus PA J Mol Biol. 2016 Oct 9;428(20):3999-4012. doi: 10.1016/j.jmb.2016.07.012. Epub, 2016 Jul 29. PMID:27477048<ref>PMID:27477048</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5i0s" style="background-color:#fffaf0;"></div> | ||
[[Category: Karplus | |||
[[Category: | ==See Also== | ||
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Driggers CM]] | |||
[[Category: Karplus PA]] | |||
[[Category: Kean KM]] | |||
Latest revision as of 11:19, 23 August 2023
Thiosulfate bound Cysteine Dioxygenase at pH 6.2Thiosulfate bound Cysteine Dioxygenase at pH 6.2
Structural highlights
FunctionPublication Abstract from PubMedIn mammals, the non-heme iron enzyme cysteine dioxygenase (CDO) helps regulate Cys levels through converting Cys to Cys sulfinic acid. Its activity is in part modulated by the formation of a Cys93-Tyr157 crosslink that increases its catalytic efficiency over 10-fold. Here, 21 high-resolution mammalian CDO structures are used to gain insight into how the Cys-Tyr crosslink promotes activity and how select competitive inhibitors bind. Crystal structures of crosslink-deficient C93A and Y157F variants reveal similar ~1.0-A shifts in the side chain of residue 157, and both variant structures have a new chloride ion coordinating the active site iron. Cys binding is also different from wild-type CDO, and no Cys-persulfenate forms in the C93A or Y157F active sites at pH6.2 or 8.0. We conclude that the crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry. In addition, structures are presented for homocysteine (Hcy), D-Cys, thiosulfate, and azide bound as competitive inhibitors. The observed binding modes of Hcy and D-Cys clarify why they are not substrates, and the binding of azide shows that in contrast to what has been proposed, it does not bind in these crystals as a superoxide mimic. Structure-Based Insights into the Role of the Cys-Tyr Crosslink and Inhibitor Recognition by Mammalian Cysteine Dioxygenase.,Driggers CM, Kean KM, Hirschberger LL, Cooley RB, Stipanuk MH, Karplus PA J Mol Biol. 2016 Oct 9;428(20):3999-4012. doi: 10.1016/j.jmb.2016.07.012. Epub, 2016 Jul 29. PMID:27477048[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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