Allosteric Inhibition via R-state Destabilization in ATP Sulfurylase from Penicillium chrysogenum
- SLAC
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 {angstrom} 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 {angstrom} 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.
- Research Organization:
- Stanford Linear Accelerator Center, Menlo Park, CA (US); Stanford Synchrotron Radiation Lab. (US)
- Sponsoring Organization:
- USDOE Office of Science (US)
- DOE Contract Number:
- AC03-76SF00515
- OSTI ID:
- 815872
- Report Number(s):
- SLAC-REPRINT-2002-277
- Journal Information:
- Nature Structural Biology, Journal Name: Nature Structural Biology
- Country of Publication:
- United States
- Language:
- English
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