Extended Data Fig. 7: The crystal structure of Cp1B likely adopts a closed active site form.
From: Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors
Comparisons of overall structures of (a) hGSH synthetase with the open active site form (3KAK), γ-glutamylcysteine is shown in magenta; (b) hGSH synthetase with closed active site form (3KAL). Mg2+ ions are shown as magenta spheres. ADP is shown in green and hGSH is shown in cyan; and (c) Cp1B in complex with adenosine shown in green and MES shown in cyan. Surface representations of the crystal structures are shown below. All structures have three characteristic domains typical of ATP-grasp enzymes: Domain A (deep salmon), Domain B (wheat), and lid domain (Domain C, cyan). P-loop (Gly-rich loop) and A-loop (Ala-rich loop) are shown in purple and blue, respectively. In the open form, the P-loop and A-loop are disordered in contrast to those in the closed form and in the Cp1B structure. Consequently, in the open form (3KAK), the nucleotide binding site open. In contrast, the lid domain with P-loop and A-loop enclose the active site in the closed form (3KAL) and partially in the Cp1B structure. These structural comparisons therefore suggested that the crystal structure of Cp1B adopts a closed active site, possibly as a result of MES binding in the active site.
