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Figure 2.
Fig. 2. Structural comparison of SERA5E and cathepsin L. (a)
Cartoon diagram of SERA5E. The N-terminal domain is to the left
and the C-terminal domain to the right of the central catalytic
cleft. The side-chain atoms of the catalytic triad, S596, H762,
and N787, are shown along with those from residues that line the
substrate-binding cleft, Q590, D594, D637, E638, S641, M643,
K701, Y703, A705, E707, R710, Y735, S816, and V818. The residues
connecting N691 to D699 in SERA5E are disordered in structures 1
and 2. (b) Cartoon diagram of cathepsin L. The side-chain atoms
of the catalytic triad in cathepsin L, C25, H163, and N187 are
highlighted, along with the side-chain atoms of A135, composing
the S[2] pocket. (c) Structural comparison of the
substrate-binding sites. The peptide backbone atoms of SERA5E
G639–S641 and cathepsin L G67–L69 are shown. The peptide
plane of G639 in structure 1 and structure 2 of SERA5E is
rotated  vert,
similar 90° compared to the orientation of the equivalent
residue in cathepsin L, whereas in structure 3, there is a
rotation of vert,
similar 45° of this and the proceeding peptide plane (S640).
The loop in the N-terminal domain leading to the strand
responsible for orienting substrates [C627–G639 and C56–G67
in SERA5E (tan) and cathepsin L (cyan), respectively] is
highlighted—this loop adopts a different path in SERA5E
compared to that in cathepsin L. The disulfide bond at the
C-terminal end of this loop is indicated. The side chains of the
catalytic-triad residues in SERA5E (S596, H762, N787) are found
in identical orientations and positions in cathepsin L (C25,
H163, N187). The S[2] pocket in cathepsin L, formed in part by
A135, is occupied by Y735 in SERA5E.
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