Differential P 1 arginine and lysine recognition in the prototypical proprotein convertase Kex2

Wheatley and Holyoak. 10.1073/pnas.0701983104.

Supporting Information

Files in this Data Supplement:

SI Figure 4
SI Table 2
SI Scheme 1

SI Figure 4

Fig. 4. Stereoview of the differential binding of lysine and arginine in the S₁ pocket. Superposing of the structures inhibited with either P₁ lysine or P₁ arginine (PDB ID code 1R64) containing inhibitors show the offset binding of lysine relative to arginine while the active site H213 and S385 positions are unchanged. The S₁ residues P275, D277, and D325 are displayed as ball-and-stick models. The P₁ lysine, H213, and S385 from the Ac-R-E-R-K-CMK (2ID4) complex are rendered as green ball-and-stick models. The P₁ arginine, H213, and S385 from the Kex2-Ac-R-E-K-R-boronic acid (PDB ID code 1R64) complex are rendered as black ball-and-stick models. The water molecule "a" and the S₁ calcium are rendered as red and gray spheres, respectively. The water molecule labeled "a" is present in the structure of Kex2 in complex with Ac-R-E-R-K-CMK (PDB ID code 2ID4) and is absent in the Kex2-Ac-R-E-K-R-boronic acid (PDB ID code 1R64) complex.

Table 2. Data and model statistics for the Ac-R-E-R-K-CMK Kex2 complex

Wavelength, Å		0.9
Space group		P6₅22
Unit cell		a = b = 112.851; c = 370.165 (Å) a = b = 90; g=120.0 (°)
Resolution limits		40.8-1.9
Unique reflections		101,674
Completeness* (%; all data)		96.6 (70.7)
Redundancy*		14.2 (2.6)
I/s_(I)*		34.2 (1.5)
R_merge^†		0.06 (0.35)
Molecules ASU		2
Solvent content. %		56.7
Amino acid residues		957
Water molecules		711
Calcium ions		4
Sodium ions		2
Carbohydrate residues		6
R_free,^‡ %	17.9
R_work,^§ %	20.7
Average B factor	30.3
Maximum likelihood based estimated coordinate error, Å	0.09
rmsd bond lengths, Å	0.008
rmsd bond angles, deg	1.145
Ramachandran statistics (most favored, additionally allowed, generously allowed, disallowed), %	89.0, 10.7, 0.4, 0

*Values in parentheses represent statistics for data in the highest-resolution shells. The highest-resolution shell comprises data in the range of 1.97-1.90 Å.

^†R_merge= ∑|I_obs - I_avg|/∑I_obs.

^‡See Brunger (1) for a description of R_free.

^§R_work= ∑ ||F_obs| - |F_calc||/∑ |F_obs|.

1. Brunger AT (1992) Nature 355:472-475.