Substrate Specificity in Thiol Dioxygenases.
Biochemistry
; 58(19): 2398-2407, 2019 05 14.
Article
in En
| MEDLINE
| ID: mdl-31045343
ABSTRACT
Thiol dioxygenases make up a class of ferrous iron-dependent enzymes that oxidize thiols to their corresponding sulfinates. X-ray diffraction structures of cysteine-bound cysteine dioxygenase show how cysteine is coordinated via its thiolate and amine to the iron and oriented correctly for O atom transfer. There are currently no structures with 3-mercaptopropionic acid or mercaptosuccinic acid bound to their respective enzymes, 3-mercaptopropionate dioxygenase or mercaptosuccinate dioxygenase. Sequence alignments and comparisons of known structures have led us to postulate key structural features that define substrate specificity. Here, we compare the rates and reactivities of variants of Rattus norvegicus cysteine dioxygenase and 3-mercaptopropionate dioxygenases from Pseudomonas aureginosa and Ralstonia eutropha (JMP134) and show how binary variants of three structural features correlate with substrate specificity and reactivity. They are (1) the presence or absence of a cis-peptide bond between residues Ser158 and Pro159, (2) an Arg or Gln at position 60, and (3) a Cys or Arg at position 164 (all RnCDO numbering). Different permutations of these features allow sulfination of l-cysteine, 3-mercaptopropionic acid, and ( R)-mercaptosuccinic acid to be promoted or impeded.
Full text:
1
Database:
MEDLINE
Main subject:
Sulfhydryl Compounds
/
Cysteine Dioxygenase
/
3-Mercaptopropionic Acid
Limits:
Animals
Language:
En
Journal:
Biochemistry
Year:
2019
Type:
Article
Affiliation country:
New Zealand