Mechanism of the human carbonic anhydrase II catalyzed hydration of carbon dioxide

Journal Article · Wed Dec 16 04:00:00 EST 1992 · Journal of the American Chemical Society; (United States)

DOI:https://doi.org/10.1021/ja00052a054· OSTI ID:6529252

Zheng, Yajun; Merz, Jr, K M ^[1]

---

1. Pennsylvania State Univ., University Park (United States)

The catalytic mechanism of human carbonic anhydrase II (HCAII) has been studied by using a combined high-level ab initio and free energy perturbation approach. The authors have examined two hydration reaction mechanisms. The first involves hydration of CO[sub 2] followed by an internal proton transfer and then loss of bicarbonate. They find that the former mechanism is more likely than the latter. On the basis of their results they have been able to predict the location of the bicarbonate proton in the recently solved X-ray structure of the HCAII-bicarbonate complex. They find that the proton is hydrogen bound to Thr-199, while one of the bicarbonate oxygens is hydrogen bound to the main-chain NH of Thr-199. This hydrogen-bonding pattern is analogous to that seen for sulfoamides, which suggests that these molecules are substrate (or transition-state) mimics. Their calculated free energy barrier for CO[sub 2] hydration is in reasonable accord with experiment, while that for the dehydration of bicarbonate is in poor agreement. The reasons for this disagreement are discussed. The molecular-level details obtained from this study have been used to construct a detailed catalytic mechanism for the mode of action of HCAII. 59 refs., 9 figs., 2 tabs.

• OSTI ID: 6529252
• Journal Information: Journal of the American Chemical Society; (United States), Journal Name: Journal of the American Chemical Society; (United States) Vol. 114:26; ISSN JACSAT; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON OXIDES
CARBON-OXYGEN LYASES
CARBONIC ANHYDRASE
CATALYSIS
CATALYTIC EFFECTS
CHALCOGENIDES
DEHYDRATION
ENERGY
ENZYMES
FREE ENERGY
HYDRATION
HYDRO-LYASES
LYASES
MATHEMATICAL MODELS
MOLECULAR MODELS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PHYSICAL PROPERTIES
PROTEINS
SOLVATION
THERMODYNAMIC PROPERTIES