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REVIEW Macromolecular juggling by ubiquitylation

By Sonja Lorenz, Aaron J Cantor, Michael Rape and John Kuriyan


The posttranslational modification of target proteins with ubiquitin and ubiquitin-like proteins is accomplished by the sequential action of E1, E2, and E3 enzymes. Members of the E1 and E3 enzyme families can undergo particularly large conformational changes during their catalytic cycles, involving the remodeling of domain interfaces. This enables the efficient, directed and regulated handover of ubiquitin from one carrier to the next one. We review some of these conformational transformations, as revealed by crystallographic studies. To catalyze multistep reactions some metabolic enzymes undergo major structural rearrangements. By disassembling the interfaces between domains and then reassembling them differently, these enzymes create distinct active sites and recognize multiple substrates sequentially. Having one enzyme that can restructure itself to carry out two or more steps in sequence is presumably more efficient than parsing out the tasks to separate enzymes and also reduces the risk of losing intermediate products, particularly those that are chemically labile. Catherine Drennan and colleagues recently introduced the term ‘molecular juggling ’ [1] to describe the large structural rearrangements of enzymes involved with B 12-dependent methyl transfer reactions [1-3]. One of us (JK) encountered a similar phenomenon in the early 1990s when studying the bacterial thioredoxin reductase enzyme [4-6]. Other examples of molecular juggling are provided by the ANL (acyl-CoA synthetases, non-ribosomal peptide synthetase adenylation domains, and luciferase) superfamily of adenylating enzymes (for review, see [7]). The last decade has seen a dramati

Year: 2013
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