2fak
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| , resolution 2.80Å | |||||||
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| Ligands: | |||||||
| Activity: | Proteasome endopeptidase complex, with EC number 3.4.25.1 | ||||||
| Related: | 1RYP, 1IRU
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome
OverviewOverview
The crystal structures of the yeast 20S proteasome core particle (CP) in complex with Salinosporamides A (NPI-0052; 1) and B (4) were solved at <3 angstroms resolution. Each ligand is covalently bound to Thr1O(gamma) via an ester linkage to the carbonyl derived from the beta-lactone ring of the inhibitor. In the case of 1, nucleophilic addition to the beta-lactone ring is followed by addition of C-3O to the chloroethyl group, giving rise to a cyclic ether. The crystal structures were compared to that of the omuralide/CP structure solved previously, and the collective data provide new insights into the mechanism of inhibition and irreversible binding of 1. Upon opening of the beta-lactone ring, C-3O assumes the position occupied by a water molecule in the unligated enzyme and hinders deacylation of the enzyme-ligand complex. Furthermore, the resulting protonation state of Thr1NH2 deactivates the catalytic N-terminus.
About this StructureAbout this Structure
2FAK is a Protein complex structure of sequences from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding., Groll M, Huber R, Potts BC, J Am Chem Soc. 2006 Apr 19;128(15):5136-41. PMID:16608349
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