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What a Role did Histidine Residue Play in Arylamine N ‐Acetyltransferase 2 Acetylation? A Quantum Chemistry Study
Author(s) -
Qiao QingAn,
Cai ZhengTing,
Yang ChuanLu,
Wang MeiShan
Publication year - 2006
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.200690237
Subject(s) - chemistry , acetylation , acetyl coa , residue (chemistry) , enzyme , histidine , cysteine , protonation , leaving group , acetyltransferases , coenzyme a , stereochemistry , catalysis , cofactor , medicinal chemistry , biochemistry , organic chemistry , ion , reductase , gene
Arylamine N ‐acetyltransferases (NATs, EC 2.3.1.5) catalyze an acetyl group transfer from acetyl coenzyme A (AcCoA) to primary arylamines and play a very important role in the metabolism and bioactivation of drugs and carcinogens. Experiments revealed that His‐107 was likely the residues responsible for mediating acetyl transfer. The full catalytic mechanism of acetylation process has been examined by density functional theory. The results indicate that, if the acetyl group is directly transferred from the donor, p ‐nitrophenyl acetate, to the acceptor, cysteine, the high activation energy will be a great hindrance. These energies have dropped in a little range of 20–25 kJ/mol when His‐107 assisted the transfer process. However, when protonated His‐107 mediated the reaction, the activation energies have been dropped about 73–85 kJ/mol. Our calculations strongly supported an enzyme acetylation mechanism that experiences a thiolate‐imidazolium pair, and verified the presumption from experiments.