5LF0

Human 20S proteasome complex with Epoxomicin at 2.4 Angstrom

Summary for 5LF0

• Entry DOI: 10.2210/pdb5lf0/pdb
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome subunit beta type-5, ... (20 entities in total)
• Functional Keywords: proteasome, multicatalytic proteinase, ntn-hydrolase, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P25787 P49721 P28074 P20618 P28070 P28072 P25789 O14818 P28066 P25786 P25788 P60900 Q99436 P49720
• Total number of polymer chains: 34
• Total formula weight: 726915.46

Authors

Schrader, J.,Henneberg, F.,Mata, R.,Tittmann, K.,Schneider, T.R.,Stark, H.,Bourenkov, G.,Chari, A. (deposition date: 2016-06-30, release date: 2016-08-17, Last modification date: 2024-03-06)

Primary citation

Schrader, J.,Henneberg, F.,Mata, R.A.,Tittmann, K.,Schneider, T.R.,Stark, H.,Bourenkov, G.,Chari, A.
The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design.
Science, 353:594-598, 2016

PubMed Abstract: The proteasome is a validated target for anticancer therapy, and proteasome inhibition is employed in the clinic for the treatment of tumors and hematological malignancies. Here, we describe crystal structures of the native human 20S proteasome and its complexes with inhibitors, which either are drugs approved for cancer treatment or are in clinical trials. The structure of the native human 20S proteasome was determined at an unprecedented resolution of 1.8 angstroms. Additionally, six inhibitor-proteasome complex structures were elucidated at resolutions between 1.9 and 2.1 angstroms. Collectively, the high-resolution structures provide new insights into the catalytic mechanisms of inhibition and necessitate a revised description of the proteasome active site. Knowledge about inhibition mechanisms provides insights into peptide hydrolysis and can guide strategies for the development of next-generation proteasome-based cancer therapeutics.

PubMed: 27493187
DOI: 10.1126/science.aaf8993

Experimental method

X-RAY DIFFRACTION (2.41 Å)