A putative Fe2+-bound persulfenate intermediate in cysteine dioxygenase.
The common reactions of dioxygen, superoxide, and hydroperoxides with thiolates are thought to proceed via persulfenate intermediates, yet these have never been visualized. Here we report a 1.4 A resolution crystal structure of the Fe(2+)-dependent enzyme cysteine dioxygenase (CDO) containing this putative intermediate trapped in its active site pocket. The complex raises the possibility that, distinct from known dioxygenases and proposed CDO mechanisms, the Fe-proximal oxygen atom may be involved in the primary oxidation event yielding a unique three-membered Fe-S-O cyclic intermediate. A nonpolar environment of the distal oxygen would facilitate isomerization of the persulfenate to the sulfinate product.
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
Chad R
CR
Simmons
Kalyanaraman
K
Krishnamoorthy
Spencer L
SL
Granett
David J
DJ
Schuller
John E
JE
Dominy
Tadhg P
TP
Begley
Martha H
MH
Stipanuk
P Andrew
PA
Karplus
D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D050558:Cysteine Dioxygenase / Q000737:chemistry* / Q000378:metabolism*; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D051381:Rats; D013434:Sulfenic Acids / Q000737:chemistry / Q000378:metabolism
D013434:Sulfenic Acids; D007501:Iron; D050558:Cysteine Dioxygenase; C100870:cysteinesulfenic acid; D003545:Cysteine