3SDK

Structure of yeast 20S open-gate proteasome with Compound 34

Summary for 3SDK

• Entry DOI: 10.2210/pdb3sdk/pdb
• Related: 3MG4 3MG6 3MG7 3MG8 3OEU 3OEV 3SDI
• Related PRD ID: PRD_001075
• Descriptor: Proteasome component Y7, Proteasome component C11, Proteasome component PRE2, ... (17 entities in total)
• Functional Keywords: 20s proteasome, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Cellular location: Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451
• Total number of polymer chains: 28
• Total formula weight: 707741.10

Authors

Sintchak, M.D. (deposition date: 2011-06-09, release date: 2012-06-13, Last modification date: 2023-09-13)

Primary citation

Blackburn, C.,Barrett, C.,Blank, J.L.,Bruzzese, F.J.,Bump, N.,Dick, L.R.,Fleming, P.,Garcia, K.,Hales, P.,Hu, Z.,Jones, M.,Liu, J.X.,Sappal, D.S.,Sintchak, M.D.,Tsu, C.,Gigstad, K.M.
Optimization of a series of dipeptides with a P3 threonine residue as non-covalent inhibitors of the chymotrypsin-like activity of the human 20S proteasome.
Bioorg.Med.Chem.Lett., 20:6581-6586, 2010

PubMed Abstract: Starting from a tripeptide screening hit, a series of dipeptide inhibitors of the proteasome with Thr as the P3 residue has been optimized with the aid of crystal structures in complex with the β-5/6 active site of y20S. Derivative 25, (β5 IC(50)=7.4 nM) inhibits only the chymotryptic activity of the proteasome, shows cellular activity against targets in the UPS, and inhibits proliferation.

PubMed: 20875739
DOI: 10.1016/j.bmcl.2010.09.032

Experimental method

X-RAY DIFFRACTION (2.7 Å)