Isomerization couples chemistry in the ATP sulfurylase-GTPase system

Jiang Wei, Thomas S. Leyh

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


ATP sulfurylase catalyzes and couples the free energies of two reactions: GTP hydrolysis and the synthesis of activated sulfate, or APS. The GTPase active site undergoes changes during its catalytic cycle that are driven by events that occur at the APS-forming active site, which is located in a separate subunit. GTP responds to its changing environment by moving along its reaction path. The response, which may change the affinity or reactivity of GTP, can, in turn, produce alterations at the APS active site that drive APS synthesis. The resulting stepwise progression of the two reactions couples their free energies. The mechanism of ATP sulfurylase involves an enzyme isomerization that precedes and rate limits cleavage of the β,γ-bond of GTP. These fluorescence studies demonstrate that the isomerization is controlled by the binding of activators that drive ATP sulfurylase into forms that mimic different stages of the APS reactions. Only certain activators elicit the isomerization, suggesting that the APS reaction must proceed to a specific point in the catalytic cycle before the conformational 'switch' that controls GTP hydrolysis is thrown. The isomerization is shown to require occupancy of the γ-phosphate subsite of the GTP binding pocket. This requirement establishes that the isomerization results in a change in the interaction between the enzyme and the γ- phosphate of GTP that emerges in the catalytic cycle during the transition from the nonisomerized to the isomerization E·GTP complex. The newly formed contact(s) appears to carry into the bond-breaking transition state, and to be essential for the enhanced affinity and reactivity of the nucleotide.

Original languageEnglish (US)
Pages (from-to)6311-6316
Number of pages6
Issue number19
StatePublished - May 11 1999

ASJC Scopus subject areas

  • Biochemistry


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