Neutron diffraction structure of (2R,3R)-L-(-)-[2-D]carnitine tetrachloroaurate, [(CH3)3N-CH2-CHOH-CHD-COOH]+[AuCl4]-: Determination of the absolute stereochemistry of the crotonobetaine-to-carnitine transformation catalyzed by L-carnitine dehydratase from Escherichia coli

Robert Bau, André Schreiber, Tobias Metzenthin, Roy S. Lu, Frank Lutz, Wim T. Klooster, Thomas F. Koetzle, Hermann Seim, Hans Peter Kleber, Curtis F. Brewer, Sasha Englard

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Single-crystal neutron diffraction has been used to determine the stereochemical course of the hydration of trans-crotonobetaine to L-(-)- carnitine by the enzyme L-carnitine dehydratase. Firstly, an X-ray analysis of the undeuterated carnitinium salt [(CH3)3N-CH2-CH(OH)-CH2- COOH]+[AuCl4]- confirmed that the absolute configuration at the C3 position of L-(-)-carnitine (the CHOH group) is indeed R. This was accomplished using the gold atom as an anomalously-scattering source. Then stereospecifically deuterated L-(-)-[2-D] carnitine was prepared by the hydration of trans-crotonobetaine in D2O using purified L-carnitine dehydratase from Escherichia coli. The subsequent neutron analysis of deuterated [(CH3)3N-CH2-CH(OH)-CH2-COOH]+ [AuCl4]- revealed that the CHD group at position C2 also had the absolute R configuration, this establishing that the addition of D2O across the C-C double bond of trans- crotonobetaine proceeds by a stereospecific syn pathway. In contrast, all other hydration-dehydration reactions examined thus far show that, when the proton added or abstracted is bonded to a carbon atom that is adjacent to a carboxylate group, the absolute stereochemistry of the resulting transformation is anti. Crystallographic details for [(CH3)3N-CH2-CH(OH)- CHD-COOH]+[AuCl4]- are as follows: space group P212121 (orthorhombic), a = 10.855-(2), b = 11.678(3), c = 22.776(6) Å; Z = 8; final agreement factor for the neutron analysis at 15 K: R(F(o)) = 0.097 based on 1140 reflections with 1 > 3σ(1).

Original languageEnglish (US)
Pages (from-to)12055-12060
Number of pages6
JournalJournal of the American Chemical Society
Volume119
Issue number50
DOIs
StatePublished - Dec 17 1997

Fingerprint

Neutron Diffraction
Hydro-Lyases
Stereochemistry
Carnitine
Neutron diffraction
Hydration
Escherichia coli
Neutrons
Atoms
X ray analysis
Dehydration
Protons
Enzymes
Gold
Single crystals
Scattering
Salts
Carbon
Statistical Factor Analysis
X-Rays

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Neutron diffraction structure of (2R,3R)-L-(-)-[2-D]carnitine tetrachloroaurate, [(CH3)3N-CH2-CHOH-CHD-COOH]+[AuCl4]- : Determination of the absolute stereochemistry of the crotonobetaine-to-carnitine transformation catalyzed by L-carnitine dehydratase from Escherichia coli. / Bau, Robert; Schreiber, André; Metzenthin, Tobias; Lu, Roy S.; Lutz, Frank; Klooster, Wim T.; Koetzle, Thomas F.; Seim, Hermann; Kleber, Hans Peter; Brewer, Curtis F.; Englard, Sasha.

In: Journal of the American Chemical Society, Vol. 119, No. 50, 17.12.1997, p. 12055-12060.

Research output: Contribution to journalArticle

Bau, Robert ; Schreiber, André ; Metzenthin, Tobias ; Lu, Roy S. ; Lutz, Frank ; Klooster, Wim T. ; Koetzle, Thomas F. ; Seim, Hermann ; Kleber, Hans Peter ; Brewer, Curtis F. ; Englard, Sasha. / Neutron diffraction structure of (2R,3R)-L-(-)-[2-D]carnitine tetrachloroaurate, [(CH3)3N-CH2-CHOH-CHD-COOH]+[AuCl4]- : Determination of the absolute stereochemistry of the crotonobetaine-to-carnitine transformation catalyzed by L-carnitine dehydratase from Escherichia coli. In: Journal of the American Chemical Society. 1997 ; Vol. 119, No. 50. pp. 12055-12060.
@article{0570a0c6d7da4559880f7cc86183c646,
title = "Neutron diffraction structure of (2R,3R)-L-(-)-[2-D]carnitine tetrachloroaurate, [(CH3)3N-CH2-CHOH-CHD-COOH]+[AuCl4]-: Determination of the absolute stereochemistry of the crotonobetaine-to-carnitine transformation catalyzed by L-carnitine dehydratase from Escherichia coli",
abstract = "Single-crystal neutron diffraction has been used to determine the stereochemical course of the hydration of trans-crotonobetaine to L-(-)- carnitine by the enzyme L-carnitine dehydratase. Firstly, an X-ray analysis of the undeuterated carnitinium salt [(CH3)3N-CH2-CH(OH)-CH2- COOH]+[AuCl4]- confirmed that the absolute configuration at the C3 position of L-(-)-carnitine (the CHOH group) is indeed R. This was accomplished using the gold atom as an anomalously-scattering source. Then stereospecifically deuterated L-(-)-[2-D] carnitine was prepared by the hydration of trans-crotonobetaine in D2O using purified L-carnitine dehydratase from Escherichia coli. The subsequent neutron analysis of deuterated [(CH3)3N-CH2-CH(OH)-CH2-COOH]+ [AuCl4]- revealed that the CHD group at position C2 also had the absolute R configuration, this establishing that the addition of D2O across the C-C double bond of trans- crotonobetaine proceeds by a stereospecific syn pathway. In contrast, all other hydration-dehydration reactions examined thus far show that, when the proton added or abstracted is bonded to a carbon atom that is adjacent to a carboxylate group, the absolute stereochemistry of the resulting transformation is anti. Crystallographic details for [(CH3)3N-CH2-CH(OH)- CHD-COOH]+[AuCl4]- are as follows: space group P212121 (orthorhombic), a = 10.855-(2), b = 11.678(3), c = 22.776(6) {\AA}; Z = 8; final agreement factor for the neutron analysis at 15 K: R(F(o)) = 0.097 based on 1140 reflections with 1 > 3σ(1).",
author = "Robert Bau and Andr{\'e} Schreiber and Tobias Metzenthin and Lu, {Roy S.} and Frank Lutz and Klooster, {Wim T.} and Koetzle, {Thomas F.} and Hermann Seim and Kleber, {Hans Peter} and Brewer, {Curtis F.} and Sasha Englard",
year = "1997",
month = "12",
day = "17",
doi = "10.1021/ja972105g",
language = "English (US)",
volume = "119",
pages = "12055--12060",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "50",

}

TY - JOUR

T1 - Neutron diffraction structure of (2R,3R)-L-(-)-[2-D]carnitine tetrachloroaurate, [(CH3)3N-CH2-CHOH-CHD-COOH]+[AuCl4]-

T2 - Determination of the absolute stereochemistry of the crotonobetaine-to-carnitine transformation catalyzed by L-carnitine dehydratase from Escherichia coli

AU - Bau, Robert

AU - Schreiber, André

AU - Metzenthin, Tobias

AU - Lu, Roy S.

AU - Lutz, Frank

AU - Klooster, Wim T.

AU - Koetzle, Thomas F.

AU - Seim, Hermann

AU - Kleber, Hans Peter

AU - Brewer, Curtis F.

AU - Englard, Sasha

PY - 1997/12/17

Y1 - 1997/12/17

N2 - Single-crystal neutron diffraction has been used to determine the stereochemical course of the hydration of trans-crotonobetaine to L-(-)- carnitine by the enzyme L-carnitine dehydratase. Firstly, an X-ray analysis of the undeuterated carnitinium salt [(CH3)3N-CH2-CH(OH)-CH2- COOH]+[AuCl4]- confirmed that the absolute configuration at the C3 position of L-(-)-carnitine (the CHOH group) is indeed R. This was accomplished using the gold atom as an anomalously-scattering source. Then stereospecifically deuterated L-(-)-[2-D] carnitine was prepared by the hydration of trans-crotonobetaine in D2O using purified L-carnitine dehydratase from Escherichia coli. The subsequent neutron analysis of deuterated [(CH3)3N-CH2-CH(OH)-CH2-COOH]+ [AuCl4]- revealed that the CHD group at position C2 also had the absolute R configuration, this establishing that the addition of D2O across the C-C double bond of trans- crotonobetaine proceeds by a stereospecific syn pathway. In contrast, all other hydration-dehydration reactions examined thus far show that, when the proton added or abstracted is bonded to a carbon atom that is adjacent to a carboxylate group, the absolute stereochemistry of the resulting transformation is anti. Crystallographic details for [(CH3)3N-CH2-CH(OH)- CHD-COOH]+[AuCl4]- are as follows: space group P212121 (orthorhombic), a = 10.855-(2), b = 11.678(3), c = 22.776(6) Å; Z = 8; final agreement factor for the neutron analysis at 15 K: R(F(o)) = 0.097 based on 1140 reflections with 1 > 3σ(1).

AB - Single-crystal neutron diffraction has been used to determine the stereochemical course of the hydration of trans-crotonobetaine to L-(-)- carnitine by the enzyme L-carnitine dehydratase. Firstly, an X-ray analysis of the undeuterated carnitinium salt [(CH3)3N-CH2-CH(OH)-CH2- COOH]+[AuCl4]- confirmed that the absolute configuration at the C3 position of L-(-)-carnitine (the CHOH group) is indeed R. This was accomplished using the gold atom as an anomalously-scattering source. Then stereospecifically deuterated L-(-)-[2-D] carnitine was prepared by the hydration of trans-crotonobetaine in D2O using purified L-carnitine dehydratase from Escherichia coli. The subsequent neutron analysis of deuterated [(CH3)3N-CH2-CH(OH)-CH2-COOH]+ [AuCl4]- revealed that the CHD group at position C2 also had the absolute R configuration, this establishing that the addition of D2O across the C-C double bond of trans- crotonobetaine proceeds by a stereospecific syn pathway. In contrast, all other hydration-dehydration reactions examined thus far show that, when the proton added or abstracted is bonded to a carbon atom that is adjacent to a carboxylate group, the absolute stereochemistry of the resulting transformation is anti. Crystallographic details for [(CH3)3N-CH2-CH(OH)- CHD-COOH]+[AuCl4]- are as follows: space group P212121 (orthorhombic), a = 10.855-(2), b = 11.678(3), c = 22.776(6) Å; Z = 8; final agreement factor for the neutron analysis at 15 K: R(F(o)) = 0.097 based on 1140 reflections with 1 > 3σ(1).

UR - http://www.scopus.com/inward/record.url?scp=0031576697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031576697&partnerID=8YFLogxK

U2 - 10.1021/ja972105g

DO - 10.1021/ja972105g

M3 - Article

AN - SCOPUS:0031576697

VL - 119

SP - 12055

EP - 12060

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 50

ER -