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==Cys-only bound Cysteine Dioxygenase at pH 9.0 in the presence of Cys== | |||
<StructureSection load='4iew' size='340' side='right' caption='[[4iew]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4iew]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ieo|4ieo]], [[4iep|4iep]], [[4ieq|4ieq]], [[4ier|4ier]], [[4ies|4ies]], [[4iet|4iet]], [[4ieu|4ieu]], [[4iev|4iev]], [[4iex|4iex]], [[4iey|4iey]], [[4iez|4iez]], [[4if0|4if0]], [[4if1|4if1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cdo1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cysteine_dioxygenase Cysteine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.20 1.13.11.20] </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=4iew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iew OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iew RCSB], [http://www.ebi.ac.uk/pdbsum/4iew PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mammalian cysteine dioxygenase (CDO) is a mononuclear non-heme iron protein that catalyzes the conversion of cysteine (Cys) to cysteine sulfinic acid by an unclarified mechanism. One structural study revealed that a Cys-persulfenate (or Cys-persulfenic acid) formed in the active site, but quantum mechanical calculations have been used to support arguments that it is not an energetically feasible reaction intermediate. Here, we report a series of high-resolution structures of CDO soaked with Cys at pH values from 4 to 9. Cys binding is minimal at pH</=5 and persulfenate formation is consistently seen at pH values between 5.5 and 7. Also, a structure determined using laboratory-based X-ray diffraction shows that the persulfenate, with an apparent average O-O separation distance of ~1.8A, is not an artifact of synchrotron radiation. At pH>/=8, the active-site iron shifts from 4- to 5-coordinate, and Cys soaks reveal a complex with Cys, but no dioxygen, bound. This 'Cys-only' complex differs in detail from a previously published 'Cys-only' complex, which we reevaluate and conclude is not reliable. The high-resolution structures presented here do not resolve the CDO mechanism but do imply that an iron-bound persulfenate (or persulfenic acid) is energetically accessible in the CDO active site, and that CDO active-site chemistry in the crystals is influenced by protonation/deprotonation events with effective pKa values near ~5.5 and ~7.5 that influence Cys binding and oxygen binding/reactivity, respectively. Furthermore, this work provides reliable ligand-bound models for guiding future mechanistic considerations. | |||
Cysteine Dioxygenase Structures from pH4 to 9: Consistent Cys-Persulfenate Formation at Intermediate pH and a Cys-Bound Enzyme at Higher pH.,Driggers CM, Cooley RB, Sankaran B, Hirschberger LL, Stipanuk MH, Karplus PA J Mol Biol. 2013 Jun 7. pii: S0022-2836(13)00358-6. doi:, 10.1016/j.jmb.2013.05.028. PMID:23747973<ref>PMID:23747973</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
==See Also== | |||
*[[Dioxygenase|Dioxygenase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cysteine dioxygenase]] | [[Category: Cysteine dioxygenase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Cooley, R B | [[Category: Cooley, R B]] | ||
[[Category: Driggers, C M | [[Category: Driggers, C M]] | ||
[[Category: Karplus, P A | [[Category: Karplus, P A]] | ||
[[Category: C93-y157 crosslink]] | [[Category: C93-y157 crosslink]] | ||
[[Category: Catalyzes oxidation]] | [[Category: Catalyzes oxidation]] | ||
Revision as of 16:19, 4 January 2015
Cys-only bound Cysteine Dioxygenase at pH 9.0 in the presence of CysCys-only bound Cysteine Dioxygenase at pH 9.0 in the presence of Cys
Structural highlights
Publication Abstract from PubMedMammalian cysteine dioxygenase (CDO) is a mononuclear non-heme iron protein that catalyzes the conversion of cysteine (Cys) to cysteine sulfinic acid by an unclarified mechanism. One structural study revealed that a Cys-persulfenate (or Cys-persulfenic acid) formed in the active site, but quantum mechanical calculations have been used to support arguments that it is not an energetically feasible reaction intermediate. Here, we report a series of high-resolution structures of CDO soaked with Cys at pH values from 4 to 9. Cys binding is minimal at pH</=5 and persulfenate formation is consistently seen at pH values between 5.5 and 7. Also, a structure determined using laboratory-based X-ray diffraction shows that the persulfenate, with an apparent average O-O separation distance of ~1.8A, is not an artifact of synchrotron radiation. At pH>/=8, the active-site iron shifts from 4- to 5-coordinate, and Cys soaks reveal a complex with Cys, but no dioxygen, bound. This 'Cys-only' complex differs in detail from a previously published 'Cys-only' complex, which we reevaluate and conclude is not reliable. The high-resolution structures presented here do not resolve the CDO mechanism but do imply that an iron-bound persulfenate (or persulfenic acid) is energetically accessible in the CDO active site, and that CDO active-site chemistry in the crystals is influenced by protonation/deprotonation events with effective pKa values near ~5.5 and ~7.5 that influence Cys binding and oxygen binding/reactivity, respectively. Furthermore, this work provides reliable ligand-bound models for guiding future mechanistic considerations. Cysteine Dioxygenase Structures from pH4 to 9: Consistent Cys-Persulfenate Formation at Intermediate pH and a Cys-Bound Enzyme at Higher pH.,Driggers CM, Cooley RB, Sankaran B, Hirschberger LL, Stipanuk MH, Karplus PA J Mol Biol. 2013 Jun 7. pii: S0022-2836(13)00358-6. doi:, 10.1016/j.jmb.2013.05.028. PMID:23747973[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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