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Figure 5.
FIG. 5. HGF  x-ray structure and Met
binding site. A, structure and electron density of HGF "active
site region." The "active site catalytic triad residues" Asp578
[c102]-Gln534 [c57]-Tyr673 [c195] are depicted. Pro693 [c215]
adopts a different conformation than Trp [c215] found in serine
proteases and partially blocks the entrance to the "S1 pocket,"
which has a Gly667 [c189] at the bottom. B, stereo view of
active site regions of HGF (green) and plasmin
(gray). The pseudo-substrate inhibitor Glu-Gly-Arg-chloromethyl
ketone from the plasmin structure (yellow) fills the S1 pocket
and interacts with its Asp [c189] side chain. The main chain
amide nitrogen atoms that stabilize the oxyanion hole (blue
spheres) are structurally conserved in HGF . C, location of Met
binding site on HGF . Worm depiction of HGF
showing mutated residues
with <20% (red), 20-60% (orange), 60-80% (yellow), and >80%
(blue) of wild type HGF pro-migratory activity data in Fig. 2B.
The N terminus and three activation domain loops are in black.
Residue Lys649 [c173] would be colored yellow but is disordered
in the crystal structure and is not depicted. D,
solvent-accessible surface of HGF showing residues colored
as in C. The dotted line depicts the Met binding region from the
crystal structure of the complex of HGF with the Sema/PSI
domains of Met (22).
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