2fak

From Proteopedia

Jump to: navigation, search


2fak, resolution 2.80Å ()
Ligands:
Activity: Proteasome endopeptidase complex, with EC number 3.4.25.1
Related: 1ryp, 1iru
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2fak is a 28 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

See Also

Reference

  • Groll M, Huber R, Potts BC. 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. J Am Chem Soc. 2006 Apr 19;128(15):5136-41. PMID:16608349 doi:10.1021/ja058320b

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools