Journal article

Direct evidence for ArO-S bond cleavage upon inactivation of Pseudomonas aeruginosa arylsulfamates by aryl sulfatase

Pavla Bojarova, Emma Denehy, Ian Walker, Karen Loft, David P De Souza, LW Lawrence Woo, Barry VL Potter, Malcolm J McConville, Spencer J Williams

CHEMBIOCHEM | WILEY-V C H VERLAG GMBH | Published : 2008

Abstract

Pseudomonas aeruginosa arylsulfatase catalyses the cleavage of aryl sulfates and is an excellent model for human estrone sulfatase, which is implicated in hormone-dependent breast cancer. Aryl sulfamates are inactivators of sulfatases; however, little is known about their mechanism. We studied the inactivation of Pseudomonas aeruginosa arylsulfatase A by a range of aryl sulfamates, including the clinical agent 667COUMATE (STX64) used to inactivate estrone sulfatase. Inactivation was time dependent, irreversible, and active-site directed, consistent with a covalent modification at the active site. In terms of the kinetic parameters of inactivation k(inact) and K(i), K(i) values are in the mic..

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