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Figure 4.
Figure 4. Secondary Substrate-Binding Pockets
(A) Two
extreme conformations of the second-site loop are shown (orange)
from RPTPγ (extended helix) and HEPTP (closed in conformation).
The catalytic cysteine is shown in a space-filling CPK
representation, and loops are colored as follows: WPD (magenta),
β5/β6 loop (green), and gateway (red). The dually pTyr
phosphorylated insulin receptor peptide (from PDB: 1G1H) is
shown superimposed (for reference only) to indicate the position
of the secondary substrate-binding pocket. The positions of
Arg24 and gateway residues Met258 and Gly259 of PTP1B are shown
in an enlarged view.
(B) Surface topology and electrostatic
charge for the active site (pY), gateway region, and secondary
pocket (2pY) are shown for each of the five categories with the
dually pTyr phosphorylated insulin receptor peptide
superimposed.
(C) Representative second-site loop
conformations are shown for each category (see also Supplemental
Data). Category I: SHP2, BDP1, LYP; Category II: IA2, IA2β;
Category III: LAR, RPTPσ; Category IV: PTPH1, MEG1, PTPD2,
CD45; Category V: STEP, HEPTP, PCPTP1.
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