Dynamic properties of the first enzymatic reaction steps of porcine pancreatic elastase. How rigid is the active site of the native enzyme? Molecular dynamics simulation

✍ Scribed by Maciej Geller; Gail Carlson-Golab; Bogdan Lesyng; Stanley M. Swanson; Edgar F. Meyer Jr.

• Publisher: Wiley (John Wiley & Sons)
• Year: 1990
• Tongue: English
• Weight: 921 KB
• Volume: 30
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360300713

✦ Synopsis

Two molecular dynamics simulations ( 100 and 50 ps) of native porcine pancreatic elastase i.e., without bound substrate and with the active site hydrated by a dome of water (630 molecules ) have been performed. Dynamical properties of the catalytic tetrad have been examined. While relative conformations of the Asp 102, His 57, and Ser 214 are rather stable in time, the side chain of Ser 195 undergoes several conformational changes. No preferences are observed for the formation of a hydrogen bond between the 0,-H group (Ser 195 ) and nitrogen N, (His 57). A cluster of ordered water molecules effectively competes with the H-0, group (Ser 195) and thereby prevents the formation of this H bond, which is generally agreed to be crucial for catalysis.

* T h e four residues, Ser 195-His 57-Asp 102-Ser 214 (chymotrypsinogen numbering system), have been uniquely iden-tified7 as being structurally conserved in all functional serine proteases (cf. Ser 221-His 64-Asp 32-Ser or Thr 33 in subtilisin).