Cation-π Interactions Contribute to Substrate Recognition in γ-Butyrobetaine Hydroxylase Catalysis

被引：23

作者：

Kamps, Jos J. A. G. ^{[1
]}

Khan, Amjad ^{[2
]}

Choi, Hwanho ^{[2
]}

Lesniak, Robert K. ^{[2
]}

Brem, Juergen ^{[2
]}

Rydzik, Anna M. ^{[2
]}

McDonough, Michael A. ^{[2
]}

Schofield, Christopher J. ^{[2
]}

Claridge, Timothy D. W. ^{[2
]}

Mecinovic, Jasmin ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Inst Mol & Mat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands

[2] Univ Oxford, Dept Chem, Chem Res Lab, 12 Mansfield Rd, Oxford OX1 3TA, England

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2016年 / 22卷 / 04期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

cation-pi interactions; C-H oxidation; enzyme catalysis; molecular recognition; oxygenases; FREE-ENERGY FUNCTION; BIOLOGICAL RECOGNITION; CARNITINE METABOLISM; GENETIC ALGORITHM; BINDING; OXYGENASES; SOLVATION; WATER;

D O I：

10.1002/chem.201503761

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

gamma-Butyrobetaine hydroxylase (BBOX) is a nonheme Fe-II- and 2-oxoglutarate-dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C-H bond of gamma-butyrobetaine (gamma BB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the gamma BB substrate. Enzyme binding and kinetic analyses on substrate analogues with P and As substituting for N in the trimethylammonium group show that the analogues are good BBOX substrates, which follow the efficiency trend N+ > P+ > As+. The results reveal that an un-charged carbon analogue of gamma BB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation-pi interactions in productive substrate recognition.

引用

页码：1270 / 1276

页数：7

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