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Figure 5.
Figure 5. Cooperativity and Molecular Mimicry in eNOS(A)
Cross talk between H[4]B and L-Arg mediated by the heme
propionate (Se-edge data). The guanidinium and amino groups of
L-Arg are held in place by H-bonding with the conserved Glu-363.
The amino group also H-bonds with a heme propionate. H[4]B
H-bonds directly with the heme propionate, while the pteridine
ring is sandwiched between Phe-462 in one monomer and Trp-449 in
another, respectively.(B) L-Arg is a structural mimic of H[4]B
at the pterin-binding site when SEITU is bound at the active
site (-H[4]B, +SEITU data). L-Arg binds to the pterin site and
exquisitely mimics the H[4]B interaction with eNOS ([A] and
Figure 4). The specific interaction of the potent inhibitor,
SEITU, at the active site is mediated by a pair of bifurcated
H-bonds to Glu-363. Two water molecules bridge between the
inhibitor and heme propionate. The ethyl group of the inhibitor
forms nonbonded contacts with Val-338 and Phe-355. The ureido
sulfur is positioned 3.5 Å and 4.0 Å above heme
pyrrole B-ring nitrogen and the heme iron, respectively.
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