Model for ligase auto-adenylylation. Mechanism of KREL1 adenylylation, representative of step 1 of ligation, in the presence of KREPA2. (Left) KREL1 (in blue) is shown with its amino terminus with five β sheets that make up the ATP binding pocket. The VLR connects the NTD to a four-helix domain at the carboxyl terminus. KREL1 begins in the open conformation with KREPA2 (in orange) αH1 bound to KREL1 αH3 CTD. (Center) In the presence of ATP in the binding pocket, the CTD is shown to fold onto its NTD in the closed conformation. The ligase catalyzes a covalent linkage between a lysine of motif I (depicted as the “K” protruding from β sheet 1) with the α-phosphate of ATP. Motif VI, KWKE, on αH4 is involved in adenylylation to form the KREL1–AMP intermediate. (Right) The ligase opens to release pyrophosphate and proceed in the ligation reaction. KREPA2's interaction mediates the conformational changes.
