Molecular mechanics evaluation of the proposed mechanisms for the degradation of urea by urease.
A thorough conformational search of all the conformations available to oxygen-bound urea within wild-type urease was carried out. Identical low energy urea conformations were obtained by a Ramachandran type plot for the NHis272-Ni1-O-Curea, and Ni1-O-Curea-Nurea dihedral angles. Ramachandran plots, with active sites and protonation states modified to model the different urease mechanisms, were used to evaluate the different mechanisms. Based upon the low energy conformations available to urea in the active site of wild-type urease one can conclude that the traditional "His320 acts as a base" mechanism is unlikely. while the N,O urea bridged and the reverse protonation mechanisms cannot be ruled out. A consensus hydrogen-bonding network that does not favor any of the mechanisms has been reconfirmed by the extensive conformational search.
Zimmer
M
M
Chemistry Department, Connecticut College, New London 06320, USA. mzim@conncoll.edu
D001051:Apoenzymes / Q000737:chemistry; D001407:Bacillus / Q000201:enzymology; D003198:Computer Simulation; D006639:Histidine / Q000378:metabolism; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D014508:Urea / Q000737:chemistry / Q000378:metabolism*; D014510:Urease / Q000378:metabolism*
D001051:Apoenzymes; D006639:Histidine; D014508:Urea; D014510:Urease