The atomic structure of crystalline porcine pancreatic elastase at 2.5 A resolution: comparisons with the structure of alpha-chymotrypsin.

Abstract Three isomorphous heavy-atom derivatives have been used to calculate a 2.5 A resolution electron density map of tosyl-elastase at pH 5.0, from which an accurate atomic model has been constructed. Atomic co-ordinates measured from this model have been refined using model building, real-space refinement and energy minimization programs. The three-dimensional conformation of the polypeptide chain is described in terms of conformational angles, hydrogen-bonding networks and the environment of different types of amino acid side-chain. Difference Fourier calculation of the high resolution structure of native elastase at pH 5.0 shows it to be virtually identical to that of the tosyl derivative, except near the tosyl group. The conformation of the catalytically important residues in native elastase is very similar to that of native α-chymotrypsin, except for the orientation of the active centre serine oxygen. The significance of important structural similarities and differences between these two enzymes is discussed. Elastase contains 25 internal water molecules which play an important role in stabilizing the active conformation of the enzyme. Many of these water molecules are in identical positions to those found in the interior of α-chymotrypsin

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