Abstract
A mutation analysis of the catalytic functions of active-site residues of coenzyme B12-dependent diol dehydratase in the conversion of 1,2-propanediol to 1,1-propanediol has been carried out by using QM/MM computations. Mutants His143Ala, Glu170Gln, Glu170Ala, and Glu170Ala/Glu221Ala were considered to estimate the impact of the mutations of His143 and Glu170. In the His143Ala mutant the activation energy for OH migration increased to 16.4 from 11.5 kcal mol-1 in the wild-type enzyme. The highest activation energy, 19.6 kcal mol-1, was measured for hydrogen back-abstraction in this reaction. The transition state for OH migration is not sufficiently stabilized by the hydrogen-bonding interaction formed between the spectator OH group and Gln170 in the Glu170Gln mutant, which demonstrates that a strong proton acceptor is required to promote OH migration. In the Glu170Ala mutant, a new strong hydrogen bond is formed between the spectator OH group and Glu221. A computed activation energy of 13.6 kcal mo-1 for OH migration in the Glu 170Ala mutant is only 2.1 kcal mol-1 higher than the corresponding barrier in the wild-type enzyme. Despite the low activation barrier, the Glu170Ala mutant is inactive because the subsequent hydrogen back-abstraction is energetically demanding in this mutant. OH migration is not feasible in the Glu170Ala/Glu221Ala mutant because the activation barrier for OH migration is greatly increased by the loss of COO- groups near the spectator OH group. This result indicates that the effect of partial deprotonation of the spectator OH group is the most important factor in reducing the activation barrier for OH migration in the conversion of 1,2-propanediol to 1,1-propanediol catalyzed by diol dehydratase.
| Original language | English |
|---|---|
| Pages (from-to) | 7864-7873 |
| Number of pages | 10 |
| Journal | Chemistry - A European Journal |
| Volume | 13 |
| Issue number | 28 |
| DOIs | |
| Publication status | Published - Oct 16 2007 |
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All Science Journal Classification (ASJC) codes
- Catalysis
- Organic Chemistry
Cite this
Computational mutation analysis of hydrogen abstraction and radical rearrangement steps in the catalysis of coenzyme B12-dependent diol dehydratase. / Kamachi, Takashi; Toraya, Tetsuo; Yoshizawa, Kazunari.
In: Chemistry - A European Journal, Vol. 13, No. 28, 16.10.2007, p. 7864-7873.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Computational mutation analysis of hydrogen abstraction and radical rearrangement steps in the catalysis of coenzyme B12-dependent diol dehydratase
AU - Kamachi, Takashi
AU - Toraya, Tetsuo
AU - Yoshizawa, Kazunari
PY - 2007/10/16
Y1 - 2007/10/16
N2 - A mutation analysis of the catalytic functions of active-site residues of coenzyme B12-dependent diol dehydratase in the conversion of 1,2-propanediol to 1,1-propanediol has been carried out by using QM/MM computations. Mutants His143Ala, Glu170Gln, Glu170Ala, and Glu170Ala/Glu221Ala were considered to estimate the impact of the mutations of His143 and Glu170. In the His143Ala mutant the activation energy for OH migration increased to 16.4 from 11.5 kcal mol-1 in the wild-type enzyme. The highest activation energy, 19.6 kcal mol-1, was measured for hydrogen back-abstraction in this reaction. The transition state for OH migration is not sufficiently stabilized by the hydrogen-bonding interaction formed between the spectator OH group and Gln170 in the Glu170Gln mutant, which demonstrates that a strong proton acceptor is required to promote OH migration. In the Glu170Ala mutant, a new strong hydrogen bond is formed between the spectator OH group and Glu221. A computed activation energy of 13.6 kcal mo-1 for OH migration in the Glu 170Ala mutant is only 2.1 kcal mol-1 higher than the corresponding barrier in the wild-type enzyme. Despite the low activation barrier, the Glu170Ala mutant is inactive because the subsequent hydrogen back-abstraction is energetically demanding in this mutant. OH migration is not feasible in the Glu170Ala/Glu221Ala mutant because the activation barrier for OH migration is greatly increased by the loss of COO- groups near the spectator OH group. This result indicates that the effect of partial deprotonation of the spectator OH group is the most important factor in reducing the activation barrier for OH migration in the conversion of 1,2-propanediol to 1,1-propanediol catalyzed by diol dehydratase.
AB - A mutation analysis of the catalytic functions of active-site residues of coenzyme B12-dependent diol dehydratase in the conversion of 1,2-propanediol to 1,1-propanediol has been carried out by using QM/MM computations. Mutants His143Ala, Glu170Gln, Glu170Ala, and Glu170Ala/Glu221Ala were considered to estimate the impact of the mutations of His143 and Glu170. In the His143Ala mutant the activation energy for OH migration increased to 16.4 from 11.5 kcal mol-1 in the wild-type enzyme. The highest activation energy, 19.6 kcal mol-1, was measured for hydrogen back-abstraction in this reaction. The transition state for OH migration is not sufficiently stabilized by the hydrogen-bonding interaction formed between the spectator OH group and Gln170 in the Glu170Gln mutant, which demonstrates that a strong proton acceptor is required to promote OH migration. In the Glu170Ala mutant, a new strong hydrogen bond is formed between the spectator OH group and Glu221. A computed activation energy of 13.6 kcal mo-1 for OH migration in the Glu 170Ala mutant is only 2.1 kcal mol-1 higher than the corresponding barrier in the wild-type enzyme. Despite the low activation barrier, the Glu170Ala mutant is inactive because the subsequent hydrogen back-abstraction is energetically demanding in this mutant. OH migration is not feasible in the Glu170Ala/Glu221Ala mutant because the activation barrier for OH migration is greatly increased by the loss of COO- groups near the spectator OH group. This result indicates that the effect of partial deprotonation of the spectator OH group is the most important factor in reducing the activation barrier for OH migration in the conversion of 1,2-propanediol to 1,1-propanediol catalyzed by diol dehydratase.
UR - http://www.scopus.com/inward/record.url?scp=35048840694&partnerID=8YFLogxK
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U2 - 10.1002/chem.200601466
DO - 10.1002/chem.200601466
M3 - Article
C2 - 17614304
AN - SCOPUS:35048840694
VL - 13
SP - 7864
EP - 7873
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 28
ER -