The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the regulated and targeted proteasome-dependent degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). Non-LEE-encoded ligase (NleL) is a member of the E3 protein ligase family and cloning of the gene from Escherichia coli was first described by Kulasekara et al. (2009). Many pathogenic bacteria can deliver virulence factors into host cells that function as E3 ligases and NleL is a bacterial ubiquitin E3 ligase involved in pedestal formation (Lin et al., 2012; Piscatelli et al., 2011). NleL has been shown to contain a cysteine residue near the C terminus of the protein that forms a transient thioester bond with Ubiquitin (Piscatelli et al., 2011). Similar to eukaryotic HECT E3s ligases, NleL functions with a subgroup of E2 enzymes that contain a conserved phenylalanine residue (Lin et al., 2010). NleL also possesses the conformational flexibility characteristic of HECT E3 ligases, however, the molecular surface of NleL bears no similarity to that of HECT E3 ligases (Daio et al., 2008; Lin et al., 2010).
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