On the dehalogenation mechanism of 4-chlorobenzoyl CoA by 4-chlorobenzoyl CoA dehalogenase: Insights from study based on the nonenzymatic reaction

被引:33
作者
Zheng, YJ [1 ]
Bruice, TC [1 ]
机构
[1] UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106
基金
英国自然环境研究理事会;
关键词
D O I
10.1021/ja970114j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The conversion of 4-chlorobenzoate to 4-hydroxybenzoate is carried out by first esterifying 4-chlorobenzoate by coenzyme A, and the resulting 4-chlorobenzoyl CoA serves as substrate for the 4-chlorobenzoyl CoA dehalogenase. To gain a better appreciation of the catalytic mechanism and factors controlling the catalytic efficacy of this dehalogenase, the nucleophilic aromatic substitution reaction between 4-Cl-Ph-CO-SCH3 and CH3COO- was investigated in detail in both gas phase and solution (the -CH2COO- entity of Asp145 is the enzyme nucleophile). Quantum mechanical methods (HF/6-31G*, B3LYP/6-311+G**, and PM3) were used to elucidate the gas phase reaction. The gas phase reaction profile is best described as a two-well potential surface, with the two minima corresponding to reactant-side and product-side ion-molecule complexes. There is a small overall potential energy barrier, but the free energy barrier is significant. On the HF/6-31G* potential energy surface, no minimum corresponding to the Meisenheimer intermediate was found; however, there is a shallow one on the PM3 surface. Overall, the PM3 results match the density functional theory results (B3LYP/6-311+G**) closely, suggesting that PM3 is a reasonable method to study this kind of reaction. This finding will allow us to investigate the enzymatic reaction directly using a hybrid PM3/MM approach. As shown from the influence of solvation effect on the reaction profile determined by a self-consistent reaction field model, there is a large reaction barrier in solution. On the basis of the above findings, the factors controlling the catalytic efficacy of the 4-chlorobenzoyl CoA dehalogenase were examined. We also studied the hydrolysis of the aryl-enzyme intermediate and a related nucleophilic aromatic substitution reaction between tetrachlorohydroquinone and glutathione (as modeled by thiomethoxide). In addition, a simple explanation concerning the previously unresolved abnormal Bronsted behavior of Tyr6Phe mutant of a mu class glutathione S-transferase is provided.
引用
收藏
页码:3868 / 3877
页数:10
相关论文
共 77 条
  • [51] NOVEL ENZYMATIC HYDROLYTIC DEHALOGENATION OF A CHLORINATED AROMATIC
    SCHOLTEN, JD
    CHANG, KH
    BABBITT, PC
    CHAREST, H
    SYLVESTRE, M
    DUNAWAYMARIANO, D
    [J]. SCIENCE, 1991, 253 (5016) : 182 - 185
  • [52] SER-HIS-GLU TRIAD FORMS THE CATALYTIC SITE OF THE LIPASE FROM GEOTRICHUM-CANDIDUM
    SCHRAG, JD
    LI, Y
    WU, S
    CYGLER, M
    [J]. NATURE, 1991, 351 (6329) : 761 - 764
  • [53] *SEM, 1994, AMPAC 5 0
  • [54] SIMKIN BY, 1993, J MOL STRUCT THEOCHE, V284, P123
  • [56] MICROBIAL DEHALOGENATION
    SLATER, JH
    BULL, AT
    HARDMAN, DJ
    [J]. BIODEGRADATION, 1995, 6 (03) : 181 - 189
  • [57] Bacterial 2-haloacid dehalogenases: Structures and catalytic properties
    Soda, K
    Kurihara, T
    Liu, JQ
    NardiDei, V
    Park, C
    Miyagi, M
    Tsunasawa, S
    Esaki, N
    [J]. PURE AND APPLIED CHEMISTRY, 1996, 68 (11) : 2097 - 2103
  • [58] CRYSTALLOGRAPHIC AND NMR-STUDIES OF THE SERINE PROTEASES
    STEITZ, TA
    SHULMAN, RG
    [J]. ANNUAL REVIEW OF BIOPHYSICS AND BIOENGINEERING, 1982, 11 : 419 - 444
  • [59] OPTIMIZATION OF PARAMETERS FOR SEMIEMPIRICAL METHODS .3. EXTENSION OF PM3 TO BE, MG, ZN, GA, GE, AS, SE, CD, IN, SN, SB, TE, HG, TL, PB, AND BI
    STEWART, JJP
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1991, 12 (03) : 320 - 341
  • [60] OPTIMIZATION OF PARAMETERS FOR SEMIEMPIRICAL METHODS .2. APPLICATIONS
    STEWART, JJP
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1989, 10 (02) : 221 - 264