4ies | pdb_00004ies

Cys-persulfenate bound Cysteine Dioxygenase at pH 6.2 in the presence of Cys

spinqualitylabelsall models 4ies, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ies is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2CO, FE Related: 4ieo, 4iep, 4ieq, 4ier, 4iet, 4ieu, 4iev, 4iew, 4iex, 4iey, 4iez, 4if0, 4if1 Gene: Cdo1 (Rattus norvegicus) Activity: Cysteine dioxygenase, with EC number 1.13.11.20 Resources: FirstGlance, OCA, RCSB, PDBsum 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase

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