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Figure 5.
Fig. 5. Crystal structure of truncated HsMetAP1 in complex
with 1 and 2. (A) Superposed is the "omit" electron density map
shown in the inhibitor binding region of compounds 1 and 2.
Coefficients are (F[o] – F[c]), where the F[o] are the
observed structure amplitudes. The calculated amplitudes F[c]
and phases are obtained from the refined model with the
inhibitors removed. The maps calculated are at 1.5 Å
(contoured at 3.6  ) for 1 and at 1.6
Å (contoured at 3.6 ) for 2. (B) Stereo
diagram showing the superposition of enzyme-inhibitor complexes
of compounds 1 (green) and 2 (magenta) in the active site pocket
of the truncated HsMetAP1 (cyano). Note that both the compounds
use a third metal ion (Co^II) in binding to the protein. Except
for the contact through the metal ion, there are no obvious
hydrogen bond contacts between the protein and the inhibitors,
although they share several hydrophobic interactions. (C) Stereo
diagram of the superposed structures of HsMetAP1 in complex with
compounds 1 and 2 and HsMetAP2 (silver). Note that Tyr-444 of
the latter enzyme experiences a severe steric clash with the
side chains of compounds 1 and 2, explaining the lower affinity
of these compounds for HsMetAP2.
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