Literature summary extracted from
Driggers, C.M.; Kean, K.M.; Hirschberger, L.L.; Cooley, R.B.; Stipanuk, M.H.; Karplus, P.A.
Structure-based insights into the role of the Cys-Tyr crosslink and inhibitor recognition by mammalian cysteine dioxygenase (2016), J. Mol. Biol., 428, 3999-4012 .
Activating Compound
EC Number |
Activating Compound |
Comment |
Organism |
Structure |
---|
1.13.11.20 |
additional information |
the enzyme activity is in part modulated by the formation of a Cys93-Tyr157 crosslink that increases its catalytic efficiency over 10fold, mechanism, overview. The crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry |
Rattus norvegicus |
|
Crystallization (Commentary)
EC Number |
Crystallization (Comment) |
Organism |
---|
1.13.11.20 |
generation of 21 CDO crystal structures at resolutions between 1.25 and 1.65 A. Of these, 16 are of C93A or Y157F CDO mutants either alone or bound to L-Cys, D-Cys, or the inhibitor homocysteine, the other five are of wild-type CDO bound to homocysteine, azide, or thiosulfate. Cys-soaked wild-type CDO crystals are analysed at pH 6.2 and pH 8.0, detailed overview |
Rattus norvegicus |
Protein Variants
EC Number |
Protein Variants |
Comment |
Organism |
---|
1.13.11.20 |
C93A |
site-directed mutagenesis, mutation of the active site residue, no crosslink formation resulting in reduced activity compared to the wild-type enzyme. The mutant variant structure has 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 active site at pH 6.2 or pH 8.0 |
Rattus norvegicus |
1.13.11.20 |
additional information |
C93A and Y157F unliganded active site structures comparison |
Rattus norvegicus |
1.13.11.20 |
Y157F |
site-directed mutagenesis, mutation of the active site residue, no crosslink formation resulting in reduced activity compared to the wild-type enzyme. The mutant variant structure has 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 Y157F active site at pH 6.2 or pH 8.0 |
Rattus norvegicus |
Inhibitors
EC Number |
Inhibitors |
Comment |
Organism |
Structure |
---|
1.13.11.20 |
azide |
competitive inhibitor, binding structure, overview. Azide does not bind in the enzyme crystal as a superoxide mimic |
Rattus norvegicus |
|
1.13.11.20 |
D-Cys |
competitive inhibitor, binding structure, overview |
Rattus norvegicus |
|
1.13.11.20 |
homocysteine |
competitive inhibitor, binding structure, overview |
Rattus norvegicus |
|
1.13.11.20 |
thiosulfate |
competitive inhibitor, binding structure, overview |
Rattus norvegicus |
|
Metals/Ions
EC Number |
Metals/Ions |
Comment |
Organism |
Structure |
---|
1.13.11.20 |
Fe2+ |
a non-heme iron enzyme |
Rattus norvegicus |
|
Natural Substrates/ Products (Substrates)
EC Number |
Natural Substrates |
Organism |
Comment (Nat. Sub.) |
Natural Products |
Comment (Nat. Pro.) |
Rev. |
Reac. |
---|
1.13.11.20 |
L-cysteine + O2 |
Rattus norvegicus |
- |
3-sulfinoalanine |
- |
? |
|
Organism
EC Number |
Organism |
UniProt |
Comment |
Textmining |
---|
1.13.11.20 |
Rattus norvegicus |
P21816 |
- |
- |
Posttranslational Modification
EC Number |
Posttranslational Modification |
Comment |
Organism |
---|
1.13.11.20 |
additional information |
the enzyme activity is in part modulated by the formation of a Cys93-Tyr157 crosslink that increases its catalytic efficiency over 10fold, mechanism, overview. The crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry |
Rattus norvegicus |
Reaction
EC Number |
Reaction |
Comment |
Organism |
Reaction ID |
---|
1.13.11.20 |
L-cysteine + O2 = 3-sulfinoalanine |
reaction mechanism |
Rattus norvegicus |
|
Substrates and Products (Substrate)
EC Number |
Substrates |
Comment Substrates |
Organism |
Products |
Comment (Products) |
Rev. |
Reac. |
---|
1.13.11.20 |
L-cysteine + O2 |
- |
Rattus norvegicus |
3-sulfinoalanine |
- |
? |
|
1.13.11.20 |
additional information |
homocysteine and D-Cys are no substrates |
Rattus norvegicus |
? |
- |
? |
|
Synonyms
EC Number |
Synonyms |
Comment |
Organism |
---|
1.13.11.20 |
CDO |
- |
Rattus norvegicus |
1.13.11.20 |
CDO1 |
- |
Rattus norvegicus |
General Information
EC Number |
General Information |
Comment |
Organism |
---|
1.13.11.20 |
additional information |
wild-type and mutant active site structures, overview |
Rattus norvegicus |
1.13.11.20 |
physiological function |
cysteine dioxygenase (CDO) helps regulate Cys levels through converting Cys to Cys sulfinic acid. The enzyme activity is in part modulated by the formation of a Cys93-Tyr157 crosslink that increases its catalytic efficiency over 10fold, mechanism, overview. The crosslink enhances activity by positioning the Tyr157 hydroxyl to enable proper Cys binding, proper oxygen binding, and optimal chemistry |
Rattus norvegicus |