Structure of native porcine pancreatic elastase at 1.65 Å resolution

Abstract
The structure of native porcine pancreatic elastase in 70% methanol has been refined using film data to 1.65 .ANG. resolution, R = 0.169. A total of 134 molecules of water (but no methanol) has been refined. This structure, because of its native state and modestly high resolution, serves as the basis for comparison with other elastase structures complexed with natural or synthetic ligands. Internal structured water occupies distinct regions. Two regions (IW1 and IW7) suggest a mechanism for equalizing ''hydrostatic pressure'' related to ligand binding and release. A third region (IW4) forms part of a hydrogen-bonding network linking the catalytic Ser 195 O.gamma. with a remote (13.4 .ANG.) surface of the enzyme. A comparison with the structures of all known serine proteases reveals that a linkage of Sero O.gamma. to remote surface is conserved in all cases, suggesting that the accepted catalytic mechanism of serine proteases needs to be re-evaluated. One possible mechanism for base catalysis of Ser O.gamma.H proton extraction is presented.