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Figure 1.
Overall crystal structure of human HdmX in complex with the
peptide-analogue Ac-Phe-Met-Aib-Pmp-Trp-Glu-Ac[3]c-Leu-NH[2]
(compound 1). A, van der Waals surface representation showing
the complex between HdmX (carbons in yellow, nitrogens in blue,
oxygens in red, and sulfurs in brown) and the p53 peptide
analogue compound 1 (ball-and-stick-model, carbons in cyan).
Selected water molecules and hydrogen bonds are shown in white.
The pockets into which Phe^19, Trp^23, and Leu^26 of p53 bind
are indicated. Compound 1 makes several water-mediated
interactions with HdmX and two direct hydrogen bonds (with
CO-Met^53 and OE1-Gln^71). The phosphonate of the Pmp residue
does not make direct interactions with HdmX. The most important
differences with Hdm2 are seen for the Leu pocket and the bottom
of the Trp pocket (Fig. 3), whereas the Phe pockets are similar.
B, chemical structures of compound 1
(Ac-Phe-Met-Aib-Pmp-Trp-Glu-Ac[3]c-Leu-NH[2]) and the derivative
compound 2, which has a 6-chlorine substituent on the indole
ring. The orientation of the chemical structure drawing is
adapted to resemble A and C, i.e. with the C terminus on the
left and the N terminus on the right. C, compound 1 fitted into
the 2F[o]-F[c] electron density map. Figs. 1, A and C, 2, and 3
were generated with PyMOL (39).
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