Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Probing structural determinants distal to the site of hydrolysis that control substrate specificity of the 20S proteasome CHEMISTRY & BIOLOGY Groll, M., Nazif, T., Huber, R., Bogyo, M. 2002; 9 (5): 655-662


    The 20S proteasome is a large multicomponent protease complex. Relatively little is known about the mechanisms that control substrate specificity of its multiple active sites. We present here the crystal structure at 2.95 A resolution of a beta2-selective inhibitor (MB1) bound to the yeast 20S proteasome core particle (CP). This structure is compared to the structure of the CP bound to a general inhibitor (MB2) that covalently modified all three (beta1, beta2, beta5) catalytic subunits. These two inhibitors differ only in their P3 and P4 residues, thereby highlighting binding interactions distal to the active site threonine that control absolute substrate specificity of the complex. Comparisons of the CP-bound structures of MB1, MB2, and the natural products epoxomycin and TMC-95A also provide information regarding general binding modes for several classes of proteasome inhibitors.

    View details for Web of Science ID 000175777800015

    View details for PubMedID 12031672

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