Nicholas J. G. Brown

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Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3(More)
Supplementary Figure 4. Characterization of the ubiquitination reactions under initial velocity conditions used to determine the apparent inhibitory constants of EMI1 variants. 15 Supplementary Figure 5. EMI1 is a tight binding inhibitor of both substrate ubiquitination and Ub chain forming activities of the APC/C CDH1 .
The Anaphase Promoting Complex/Cyclosome (APC/C) is a ~1.5 MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell cycle regulatory proteins. Inhibition of human APC/C CDH1 during interphase by Early Mitotic Inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and(More)
The anaphase-promoting complex/cyclosome bound to CDC20 (APC/C CDC20) initiates anaphase by ubiquitylating B-type cyclins and securin. During chromosome bi-orientation, CDC20 assembles with MAD2, BUBR1 and BUB3 into a mitotic checkpoint complex (MCC) which inhibits substrate recruitment to the APC/C. APC/C activation depends on MCC disassembly, which has(More)
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