Figure 4.The Active Site of TG2 and Enzyme–Inhibitor
(A) Electrostatic potential surface of TG2
(red indicates negative charge; blue, positive; contoured at
−15 k[B]T to +15 k[B]T) in the vicinity of the peptide
inhibitor. (Carbon is indicated by cyan; nitrogen by blue; and
oxygen by red.)
(B) Surface representation of the
active-site tryptophan bridge. W332, W241, and inhibitor are
shown in green, red, and cyan, respectively. The proposed
acyl-acceptor approach site is indicated.
representation of the active site of TG2. The backbone of TG2 is
shown as ribbons. The bridge tryptophans and a T360 that resides
in front of the proposed acyl-acceptor entrance are shown as
sticks with semitransparent surfaces. It can be seen that the
bridging tryptophan residues reside on separate loops above the
catalytic Cys (sulfur is indicated by yellow). The thioether
attachment of the inhibitor (cyan indicates inhibitor carbons,
and gray indicates TG2 carbons) is also evident.
Hydrogen-bonding interactions between TG2 and the peptide are
shown as dashed lines.
(E) Schematic diagram of hydrophobic
interactions between TG2 and the inhibitor.
The above figure is reprinted
from an Open Access publication published by Public Library of Science: