TY - JOUR
T1 - A quantum chemical study of the synthesis of prostaglandin G2 by the cyclooxygenase active site in prostaglandin endoperoxide H synthase 1
AU - Blomberg, L. Mattias
AU - Blomberg, Margareta R.A.
AU - Siegbahn, Per E.M.
AU - Van der Donk, Wilfred A.
AU - Tsai, Ah Lim
PY - 2003/4/10
Y1 - 2003/4/10
N2 - The mechanism for prostaglandin G2 synthesis in the cyclooxygenase active site of prostaglandin H synthase has been investigated using hybrid density functional theory (B3LYP). The calculations show that the six-step radical mechanism for the transformation of arachidonic acid to prostaglandin G2 suggested by Hamberg and Samuelsson is energetically feasible. The overall driving force for the reaction starting with the arachidonic acid and the active-site tyrosyl radical is estimated to be about 37 kcal/mol, and two barriers are found to be about 15 kcal/mol, in good agreement with the experimental rate corresponding to a barrier of 14.8 kcal/mol. Competing reactions are also investigated.
AB - The mechanism for prostaglandin G2 synthesis in the cyclooxygenase active site of prostaglandin H synthase has been investigated using hybrid density functional theory (B3LYP). The calculations show that the six-step radical mechanism for the transformation of arachidonic acid to prostaglandin G2 suggested by Hamberg and Samuelsson is energetically feasible. The overall driving force for the reaction starting with the arachidonic acid and the active-site tyrosyl radical is estimated to be about 37 kcal/mol, and two barriers are found to be about 15 kcal/mol, in good agreement with the experimental rate corresponding to a barrier of 14.8 kcal/mol. Competing reactions are also investigated.
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U2 - 10.1021/jp027204h
DO - 10.1021/jp027204h
M3 - Article
AN - SCOPUS:0037431334
SN - 1089-5647
VL - 107
SP - 3297
EP - 3308
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 14
ER -