FIGURE 3 | Ubiquitin-activating enzymes as potential pharmacological targets.

From the following article:

Drug discovery in the ubiquitin–proteasome system

Grzegorz Nalepa, Mark Rolfe and J. Wade Harper

Nature Reviews Drug Discovery 5, 596-613 (July 2006)

doi:10.1038/nrd2056

Drug discovery in the ubiquitin|[ndash]|proteasome system

a | The NEDD8-activating enzyme (E1NEDD8) is composed of UBA3 and APPBP1. In the presence of ATP, NEDD8 is activated through formation of a thiol ester, which is then transferred to UBC12. UBC12 transfers NEDD8 to a single lysine residue in the cullin proteins to form an isopeptide linkage. b | Organization of the APPBP1/UBA3 heterodimer and comparison of the domain structures of E1NEDD8 with E1Ub. c | Structure of the E1NEDD8 complex bound to NEDD8 (APPBP1 is shown in yellow, UBA3 in magenta, NEDD8 in pink). ATP (space-filled) is buried in the adenylation pocket and is located near the carboxy-terminal glycine residue of NEDD8. d | The ubiquitin-like domain of E1NEDD8 (magenta; see panel b) uses a beta-sheet surface common to all ubiquitin folds to bind to UBC12 (yellow). The catalytic cysteine of UBC12 is shown in a space-filled model. APPB1, amyloid-beta precursor protein binding protein 1; NEDD, neural precursor cell expressed, developmentally down-regulated; UBA, ubiquitin-activating enzyme.

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