The Hydrolysis of Urea and the Proficiency of Urease
- 7 May 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 126 (22), 6932-6944
- https://doi.org/10.1021/ja049327g
Abstract
We present the results of a computational study of the solution phase decomposition of urea, which provides insight into probable reaction pathways for the urease-catalyzed reaction. Calculations, which were used to derive thermodynamic parameters that were further used for a kinetic analysis, have been done at the solvent-corrected MP2/6-311++G** level. Both elimination and hydrolytic pathways have been considered. Elimination is favored for the solution phase reaction, which proceeds by H-bond coordination of a water molecule to the amine nitrogen atoms. The coordination of one water molecule greatly facilitates the reaction by allowing it to proceed through a cyclic six-member transition state. Aspects of the water−urea H-bond interactions have also provided insights into critical aspects of the hydrogen bond pattern in the urease active site. On the basis of a kinetic analysis, we have estimated the proficiency of urease and have predicted that it is the most proficient enzyme identified to date.This publication has 39 references indexed in Scilit:
- Supramolecular assembly and acid resistance of Helicobacter pylori urease.Nature Structural & Molecular Biology, 2001
- Fluoride Inhibition of Klebsiella aerogenes Urease: Mechanistic Implications of a Pseudo-uncompetitive, Slow-Binding InhibitorBiochemistry, 2000
- Helicobacter pylori Virulence and Genetic GeographyScience, 1999
- Chemical Rescue of Klebsiella aerogenes Urease Variants Lacking the Carbamylated-Lysine Nickel Ligand,Biochemistry, 1998
- 70 Years of Crystalline Urease: What Have We Learned?Accounts of Chemical Research, 1997
- Structures of the Klebsiella aerogenes Urease Apoenzyme and Two Active-Site Mutants,Biochemistry, 1996
- Molecular biology of microbial ureasesMicrobiological Reviews, 1995
- Jack bean urease (EC 3.5.1.5). Metalloenzyme. Simple biological role for nickelJournal of the American Chemical Society, 1975
- Kinetic Studies of Thiourea Derivatives. IV. The Methylated Thioureas. Conclusions1Journal of the American Chemical Society, 1958
- The Molecular Kinetics of the Urea-Urease System. III. Heats and Entropies of Complex Formation and Reaction1Journal of the American Chemical Society, 1950