Allosteric inhibition via R-state destabilization in ATP sulfurylase from Penicillium chrysogenum

Ian J. MacRae, Irwin H. Segel, Andrew J Fisher

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The structure of the cooperative hexameric enzyme ATP sulfurylase from Penicillium chrysogenum bound to its allosteric inhibitor, 3′-phosphoadenosine-5′-phosphosulfate (PAPS), was determined to 2.6 Å resolution. This structure represents the low substrate-affinity T-state conformation of the enzyme. Comparison with the high substrate-affinity R-state structure reveals that a large rotational rearrangement of domains occurs as a result of the R-to-T transition. The rearrangement is accompanied by the 17 Å movement of a 10-residue loop out of the active site region, resulting in an open, product release-like structure of the catalytic domain. Binding of PAPS is proposed to induce the allosteric transition by destabilizing an R-state-specific salt linkage between Asp 111 in an N-terminal domain of one subunit and Arg 515 in the allosteric domain of a trans-triad subunit. Disrupting this salt linkage by site-directed mutagenesis induces cooperative inhibition behavior in the absence of an allosteric effector, confirming the role of these two residues.

Original languageEnglish (US)
Pages (from-to)945-949
Number of pages5
JournalNature Structural Biology
Issue number12
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics


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