Cation-π interactions contribute to substrate recognition in γ-butyrobetaine hydroxylase catalysis

Jos J.A.G. Kamps, Amjad Khan, Hwanho Choi, Robert K. Lesniak, Jürgen Brem, Anna M. Rydzik, Michael A. McDonough, Christopher J. Schofield, Timothy D.W. Claridge, Jasmin Mecinovic*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

γ-Butyrobetaine hydroxylase (BBOX) is a non-heme FeII- and 2-oxoglutarate-dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C-H bond of γ-butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB 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 uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation-π interactions in productive substrate recognition. What's in the BBOX? Enzyme kinetics and substrate binding studies reveal that γ-butyrobetaine hydroxylase (BBOX)-catalyzed stereoselective hydroxylation of γ-butyrobetaine involves energetically favorable cation-π interactions.

OriginalsprogEngelsk
TidsskriftChemistry - A European Journal
Vol/bind22
Udgave nummer4
Sider (fra-til)1270-1276
ISSN0947-6539
DOI
StatusUdgivet - 22. jan. 2016
Udgivet eksterntJa

Fingeraftryk

Cations
Hydroxylation
Oxygenases
Enzymes
gamma-butyrobetaine

Citer dette

Kamps, Jos J.A.G. ; Khan, Amjad ; Choi, Hwanho ; Lesniak, Robert K. ; Brem, Jürgen ; Rydzik, Anna M. ; McDonough, Michael A. ; Schofield, Christopher J. ; Claridge, Timothy D.W. ; Mecinovic, Jasmin. / Cation-π interactions contribute to substrate recognition in γ-butyrobetaine hydroxylase catalysis. I: Chemistry - A European Journal. 2016 ; Bind 22, Nr. 4. s. 1270-1276.
@article{b7f357437aa2460087f9cadb79f2b092,
title = "Cation-π interactions contribute to substrate recognition in γ-butyrobetaine hydroxylase catalysis",
abstract = "γ-Butyrobetaine hydroxylase (BBOX) is a non-heme FeII- and 2-oxoglutarate-dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C-H bond of γ-butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB 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 uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation-π interactions in productive substrate recognition. What's in the BBOX? Enzyme kinetics and substrate binding studies reveal that γ-butyrobetaine hydroxylase (BBOX)-catalyzed stereoselective hydroxylation of γ-butyrobetaine involves energetically favorable cation-π interactions.",
keywords = "C-H oxidation, cation-pi interactions, enzyme catalysis, molecular recognition, oxygenases",
author = "Kamps, {Jos J.A.G.} and Amjad Khan and Hwanho Choi and Lesniak, {Robert K.} and J{\"u}rgen Brem and Rydzik, {Anna M.} and McDonough, {Michael A.} and Schofield, {Christopher J.} and Claridge, {Timothy D.W.} and Jasmin Mecinovic",
year = "2016",
month = "1",
day = "22",
doi = "10.1002/chem.201503761",
language = "English",
volume = "22",
pages = "1270--1276",
journal = "Chemistry: a European Journal",
issn = "0947-6539",
publisher = "Wiley-VCH",
number = "4",

}

Kamps, JJAG, Khan, A, Choi, H, Lesniak, RK, Brem, J, Rydzik, AM, McDonough, MA, Schofield, CJ, Claridge, TDW & Mecinovic, J 2016, 'Cation-π interactions contribute to substrate recognition in γ-butyrobetaine hydroxylase catalysis', Chemistry - A European Journal, bind 22, nr. 4, s. 1270-1276. https://doi.org/10.1002/chem.201503761

Cation-π interactions contribute to substrate recognition in γ-butyrobetaine hydroxylase catalysis. / Kamps, Jos J.A.G.; Khan, Amjad; Choi, Hwanho; Lesniak, Robert K.; Brem, Jürgen; Rydzik, Anna M.; McDonough, Michael A.; Schofield, Christopher J.; Claridge, Timothy D.W.; Mecinovic, Jasmin.

I: Chemistry - A European Journal, Bind 22, Nr. 4, 22.01.2016, s. 1270-1276.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Cation-π interactions contribute to substrate recognition in γ-butyrobetaine hydroxylase catalysis

AU - Kamps, Jos J.A.G.

AU - Khan, Amjad

AU - Choi, Hwanho

AU - Lesniak, Robert K.

AU - Brem, Jürgen

AU - Rydzik, Anna M.

AU - McDonough, Michael A.

AU - Schofield, Christopher J.

AU - Claridge, Timothy D.W.

AU - Mecinovic, Jasmin

PY - 2016/1/22

Y1 - 2016/1/22

N2 - γ-Butyrobetaine hydroxylase (BBOX) is a non-heme FeII- and 2-oxoglutarate-dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C-H bond of γ-butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB 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 uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation-π interactions in productive substrate recognition. What's in the BBOX? Enzyme kinetics and substrate binding studies reveal that γ-butyrobetaine hydroxylase (BBOX)-catalyzed stereoselective hydroxylation of γ-butyrobetaine involves energetically favorable cation-π interactions.

AB - γ-Butyrobetaine hydroxylase (BBOX) is a non-heme FeII- and 2-oxoglutarate-dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C-H bond of γ-butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB 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 uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation-π interactions in productive substrate recognition. What's in the BBOX? Enzyme kinetics and substrate binding studies reveal that γ-butyrobetaine hydroxylase (BBOX)-catalyzed stereoselective hydroxylation of γ-butyrobetaine involves energetically favorable cation-π interactions.

KW - C-H oxidation

KW - cation-pi interactions

KW - enzyme catalysis

KW - molecular recognition

KW - oxygenases

UR - http://www.scopus.com/inward/record.url?scp=84954381267&partnerID=8YFLogxK

U2 - 10.1002/chem.201503761

DO - 10.1002/chem.201503761

M3 - Journal article

VL - 22

SP - 1270

EP - 1276

JO - Chemistry: a European Journal

JF - Chemistry: a European Journal

SN - 0947-6539

IS - 4

ER -