Premium
Elucidating the mechanism for the reduction of nitrite by copper nitrite reductase—A contribution from quantum chemical studies
Author(s) -
De Marothy S. A.,
Blomberg M. R. A.,
Siegbahn P. E. M.
Publication year - 2006
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20567
Subject(s) - chemistry , nitrite , protonation , catalysis , catalytic cycle , active site , nitrite reductase , substrate (aquarium) , histidine , nitric oxide , ligand (biochemistry) , inorganic chemistry , photochemistry , computational chemistry , enzyme , organic chemistry , nitrate , biochemistry , ion , oceanography , receptor , geology
Density functional methods have been applied to investigate the properties of the active site of copper‐containing nitrite reductases and possible reaction mechanisms for the enzyme catalysis. The results for a model of the active site indicate that a hydroxyl intermediate is not formed during the catalytic cycle, but rather a state with a protonated nitrite bound to the reduced copper. Electron affinity calculations indicate that reduction of the T2 copper site does not occur immediately after nitrite binding. Proton affinity calculations are indicative of substantial p K a differences between different states of the T2 site. The calculations further suggest that the reaction does not proceed until uptake of a second proton from the bulk solution. They also indicate that Asp‐92 may play both a key role as a proton donor to the substrate, and a structural role in promoting catalysis. In the D92N mutant another base, presumably a nearby histidine (His‐249) may take the role as the proton donor. On the basis of these model calculations and available experimental evidence, an ordered reaction mechanism for the reduction of nitrite is suggested. An investigation of the binding modes of the nitric oxide product and the nitrite substrate to the model site has also been made, indicating that nitric oxide prefers to bind in an end‐on fashion to the reduced T2 site. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 528–539, 2007