|
Figure 3.
Figure 3. Crystal structure of the binary complex between cIRK
and the bisubstrate inhibitor. a, Overall view of the binary
complex in which cIRK is shown in surface representation and the
bisubstrate inhibitor in stick representation. The ATP  S
moiety of the inhibitor is colored green, the peptide moiety is
colored red, and the linker connecting the nucleotide and
peptide is colored yellow. The cIRK surface is semi-transparent;
the N-terminal lobe of cIRK partially masks the nucleotide. b,
Stereo view of the F[o] - F[c] electron density (2.7 Å
resolution, 3  contour)
for the bisubstrate inhibitor computed after simulated annealing
(1,000 K), omitting from the atomic model either ATP S
+ linker (blue map) or the peptide moiety (green map). Coloring
of the bisubstrate inhibitor is the same as in (a). Selected
peptide residues are labeled; Y'(P0) refers to the modified Tyr
at the P0 position of the peptide. The purple sphere represents
the Mg2+ and the red sphere represents the Mg2+-coordinating
water molecule. c, Stereo view of the interactions between the
inhibitor and key catalytic residues. Superimposed are the cIRK
-bisubstrate inhibitor (binary) complex and the cIRK -MgAMP-PNP
-peptide (ternary) complex15. Oxygen atoms are colored red,
nitrogen atoms blue, sulfur atoms green, and phosphorus atoms
yellow. Bonds/carbon atoms are colored orange for the binary
complex and green for the ternary complex. Bonds and atoms of
the ternary complex are semi-transparent. Mg2+ ions and water
molecules are represented as purple and red spheres,
respectively. Hydrogen bonds and bonds to the Mg2+ are
represented as dashed and solid black lines, respectively. Only
the modified tyrosine from the peptide moiety of the inhibitor
is shown. 'BSI' indicates the bisubstrate inhibitor in the
binary complex, and 'Y(P0)' and 'PNP' indicate the substrate
tyrosine and AMP-PNP, respectively, in the ternary complex.
Selected secondary structural elements (  C
and  3)
are shown. The figure was prepared with GRASP28, BOBSCRIPT29 and
MOLSCRIPT30.
|
