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H/D exchange revealed the distribution of flexible and rigid regions of α1AT, whereas footprinting revealed the dynamic environments of several side chains previously identified as important for the metastability of α1AT.
Several side chains in hinge 1 (colored pink) also exhibit rotamer averaging.
In addition, R69 also takes part in the stacking of several side chains, i.e. R61, W30, R69 and Y73, which certainly participates to the 3D structure arrangement of the R2 domain.
Residues 34-892 were assigned in the final model, however, several side chains were not placed due to the weak electron density, specifically in the EF-hands 1-2.
In the model of the Sirt2 complex with 3, hydrophobic interactions are observed between the estradiol ring system and several side chains (Phe96, Leu107, Phe119 and Ile169) of a large, hydrophobic cavity (formed by the interacting residues and Ala85, Tyr104, and Ile118) extending into the small Sirtuin Zn2+-domain.
Comparison of these five structures to that of CaS100B (PDB entry 1MHO(47)) with no drug target reveals a strong conservation of the global fold (Table 3); however, deviations in the positions of several side chains in the target binding site of CaS100B were observed, as necessary, to accommodate the binding of various SBi X molecules.
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Assignment of each pick was consistent with an alkane structure back bone bearing several side chain modifications (Figure 3a).
To avoid steric clashes the several side chain positions were corrected manually using the Xfit program (www.sdcs.edu/CCMS/Packages/XTALVIEW/xtalview.html).html
Yes, several side chain rotamers exhibit differences from the 1.9 Å X-ray structure.
It leads to slight uncertainty in the position of several side chain residues, including the inserted Asp, Thr347, and His348.
There are several backbone carbonyl groups (His-83, Glu-105, Glu-106) and several side chain groups (Arg-107 and Arg-116) in proximity to His-104 in members of the solution ensemble.
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