(a) CMP–SiaFAc (from 5BO9, green carbons) was superposed onto cocrystalized
CMP in the ST6Gal-I binding pocket (4JS2, white carbons and surface). Distances
(Å) to nearest residues Gln235, Tyr354, and Phe359 are indicated
with black dashes. (b) Cocrystalized CMP–Sia (green carbons)
in the CMAS binding pocket (1QWJ, domain D, white carbons). Between the HC (Leu121,
Ile124, Tyr216, and Leu228) and the sialic acid pyranose ring, there
is a hydrophilic gate (Ser120, Gln141, pink carbons). Hydrogen bonds
are depicted with orange lines. (c,d) Energy-minimized poses of SiaFPen
(6) [green carbons, (c)] and SiaFPoc (7)
[green carbons, (d)] in the CMAS binding pocket (1QWJ, domain D, white
carbons). Hydrogen bonds are depicted with orange lines. The hydrophilic
gate accommodates the carbamate [SiaFPoc, (d)] more favorably than
the amide [SiaFPen, (c)] because of an additional polar interaction
with Ser120.