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Divide and conquer: the E2 active site

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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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Figure 1: Schematic view of the multistep process of protein modification, showing the transfer of ubiquitin(-like) proteins (yellow) from E1 to E2 and then, with the help of an E3, to the target.
Figure 2: Divided activation of the target lysine.

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Authors and Affiliations

  1. Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands

    Puck Knipscheer & Titia K Sixma

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  1. Puck Knipscheer
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  2. Titia K Sixma
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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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