5lf3
From Proteopedia
Human 20S proteasome complex with Bortezomib at 2.1 Angstrom
Structural highlights
FunctionPSA2_HUMAN The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. Publication Abstract from PubMedThe 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. The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design.,Schrader J, Henneberg F, Mata RA, Tittmann K, Schneider TR, Stark H, Bourenkov G, Chari A Science. 2016 Aug 5;353(6299):594-8. doi: 10.1126/science.aaf8993. PMID:27493187[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Bourenkov G | Chari A | Henneberg F | Mata R | Schneider TR | Schrader J | Stark H | Tittmann K
