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Theoretical study of carbonic anhydrase‐catalyzed hydration of co 2 : A brief review
Author(s) -
Liang JiinYun,
Lipscomb William N.
Publication year - 1989
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560360313
Subject(s) - chemistry , intramolecular force , catalysis , proton , zinc , nucleophile , aqueous solution , carbonic anhydrase , carbonic anhydrase ii , molecule , ligand (biochemistry) , bound water , crystallography , inorganic chemistry , stereochemistry , enzyme , organic chemistry , receptor , biochemistry , physics , quantum mechanics
Quantum mechanical calculations have been used to study the reaction mechanism of human carbonic anhydrase‐catalyzed hydration of CO 2 . This reaction is responsible for fast metabolism of CO 2 in the human body. For each of the reaction steps, possible catalytic effects of active site residues are examined. The pertinent results are as follows. (1) For CO 2 binding, the experimentally observed 2.5 cm −1 frequency shift of the asymmetic stretching frequency between measurements taken in the aqueous solution and in the enzyme is reproduced in our theoretical calculations. Our results suggest that CO 2 binds to the zinc ion within the hydrophobic pocket. (2) No energy barrier is found for the nucleophilic attack from Zn 2+ −bound OH − to C of CO 2 to form Zn 2+ −bound HCO 3 − . (3) For the internal proton transfer within zinc‐bound HCO 3 − , the barrier of 35.6 kcal/mol for the direct internal proton transfer is reduced to 3.5 and 1.4 kcal/mol, respectively, when one or two water molecules are included for proton relay. (4) Displacement of Zn 2+ −bound HCO 3 − by H 2 O is facilitated by the presence of the negatively charged Glu 106‐Thr 199 chain and by the association and the subsequent ionization of a fifth water ligand. (5) For the intramolecular proton transfer between Zn 2+ ‐bound H 2 O and His 64, the Zn 2+ ion lowers the pK a of Zn 2+ −bound water and repels the proton. His 64, or a similar proton receptor with a larger proton affinity than H 2 O, functions as proton receiver; and the active site water molecules visualized by x‐ray crystallography are important for the proton relay function. In summary, it is demonstrated that in order to achieve effective catalysis, a sequence of precisely coordinated catalytic events among all participating catalytic elements in the enzyme's active site is essential.