|
Figure 2.
Co-crystallization of deacetylated 1 with the open form of
the human enzyme, hM340H-Gal-T1. a, binding of deacetylated 1 to
the catalytic domain of β4Gal-T1, in the presence of Mn^2+
(purple sphere) and UDP-hexanolamine (UDP-H). The β4Gal-T1
molecule is found in the closed conformation with its Trp-310
side chain (red) placed inside the catalytic pocket, interacting
with the phosphate oxygen atom of UDP-hexanolamine molecule,
whereas the long flexible loop (blue) covers the
UDP-hexanolamine and exposes the acceptor binding site to
facilitate binding to the enzyme. b, the molecular interactions
of deacetylated 1 (blue) with the β4Gal-T1 (green). The
hydrogen bonds are shown in black dotted lines. The GlcNAc
moiety of deacetylated 1 is bound in the acceptor sugar binding
site. The Gal residue forms hydrophobic interactions with the
aromatic side chain of the Tyr-282 residue, whereas the
naphthalenemethanol extends out of the sugar binding site,
weakly interacting with the β4Gal-T1 molecule. There is a
structural water molecule (W) indicated with black dotted lines
that, in addition to forming a hydrogen bond with the side-chain
amino group of Arg-355, bridges the GlcNAc and Gal via hydrogen
bonds. c, molecular surface (van der Waals) diagram showing the
binding of deacetylated trisaccharide
GlcNAcβ1–2Manα1–6Manβ-O-R (where R represents
-CH[2]–CH[2]–CH[2]–CH=CH[2] (15)) to β4Gal-T1 (light
blue). d, molecular surface (van der Waals) diagram showing the
binding of deacetylated disaccharide 1 to β4Gal-T1 (light
blue). e, superposition of the bound deacetylated disaccharide 1
(blue) with the bound trisaccharide,
GlcNAcβ1–2Manα1–6Manβ-O-R (yellow) in the respective
acceptor substrate complexes with β4Gal-T1 (blue).
|
