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Literature summary for 3.5.3.18 extracted from

  • Johnson, C.M.; Linsky, T.W.; Yoon, D.W.; Person, M.D.; Fast, W.
    Discovery of halopyridines as quiescent affinity labels: inactivation of dimethylarginine dimethylaminohydrolase (2011), J. Am. Chem. Soc., 133, 1553-1562.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
A 2.18 A resolution X-ray crystal structure of the inactivated complex elucidates the orientation of the inactivator and its covalent attachment to the active site Cys Pseudomonas aeruginosa

Protein Variants

Protein Variants Comment Organism
C249S the C249S mutant and D66N mutant are both incapable of forming a covalent adduct when incubated with 2-hydroxymethyl-4-chloropyridine Pseudomonas aeruginosa
D244N wild type and D244N DDAH variants both form covalent adducts upon incubation with 2-hydroxymethyl-4-chloropyridine, showing mass additions that are consistent with covalent attachment of one equivalent of hydroxymethylpyridine to each enzyme. These results also indicate that Asp244 is not essential for covalent modification to occur Pseudomonas aeruginosa
D66N the C249S mutant and D66N mutant are both incapable of forming a covalent adduct when incubated with 2-hydroxymethyl-4-chloropyridine Pseudomonas aeruginosa
S248N mutant is still capable of substrate turnover and is still inactivated by 2-hydroxymethyl-4-chloropyridine with a second order inactivation rate constant that is approximately 2fold less than wild type DDAH Pseudomonas aeruginosa

Inhibitors

Inhibitors Comment Organism Structure
2-hydroxymethyl-4-chloropyridine solution studies support an inactivation mechanismin in which the active site Asp66 residue stabilizes the pyridinium form of the inactivator, which has enhanced reactivity toward the active site Cys, resulting in covalent bond formation, loss of the halide, and irreversible inactivation Pseudomonas aeruginosa

Organism

Organism UniProt Comment Textmining
Pseudomonas aeruginosa
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Synonyms

Synonyms Comment Organism
dimethylarginine dimethylaminohydrolase
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Pseudomonas aeruginosa