JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome
Figure 3
Metalloprotease-Like Active Site of AfJAMM
(A) The active site of AfJAMM is shown centered around the catalytic zinc ion, which is represented as a dark gray sphere surrounded by anomalous cross Fourier difference density (contoured at 9.5 σ) colored in red. The aqua ligand, which lies at 2.9 Å from the zinc, is shown as a red sphere surrounded by purple density (contoured at 3 σ) of an Fobs – Fcalc map, in which the aqua ligand was omitted from the calculation. Residues that underlie isopeptide bond cleavage are shown in green. The carboxylate oxygen atoms of D80 lie 2.2 Å from the zinc. The Nε2 atoms of H67 and H69 lie 2.1 Å from the zinc. The carboxylate oxygen atoms of E22 lie 3.2–3.5 Å from the aqua ligand and 4.5–5.0 Å from the zinc. Ancillary active site residues and the backbone (ribbon diagram) are shown in grey. The disulfide bond that links C74 to C95 is shown in yellow. The JAMM motif is shown in the upper lefthand corner for reference.
(B) Superimposition of active site residues in ScNP, thermolysin, and AfJAMM. AfJAMM is in green, ScNP in blue, and thermolysin in red. For clarity only, the sidechains from the residues that bind the zinc or aqua ligands are shown in their entirety. In addition, atoms that stabilize the putative tetrahedral intermediate are shown. These include Oγ of S77 in AfJAMM, Oη of Y95 in ScNP, and the Nε2 of H231 in thermolysin.