The E2 enzymes for ubiquitin and SUMO conjugation share a conserved active site that has long been mysterious for lack of identifiable catalytic residues. In an elegant tour de force, it is now shown how three E2 residues not only position the target lysine but also substantially lower its pK to allow deprotonation and efficient substrate transfer.
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E2 superfamily of ubiquitin-conjugating enzymes: constitutively active or activated through phosphorylation in the catalytic cleft
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Knipscheer, P., Sixma, T. Divide and conquer: the E2 active site. Nat Struct Mol Biol 13, 474–476 (2006). https://doi.org/10.1038/nsmb0606-474
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DOI: https://doi.org/10.1038/nsmb0606-474