Analysis of UDP-D-apiose/UDP-D-xylose synthase-catalyzed conversion of UDP-D-apiose phosphonate to UDP-D-xylose phosphonate: Implications for a retroaldol-aldol mechanism

Sei Hyun Choi, Steven O. Mansoorabadi, Yung Nan Liu, Tun Cheng Chien, Hung Wen Liu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

UDP-d-apiose/UDP-d-xylose synthase (AXS) catalyzes the conversion of UDP-d-glucuronic acid to UDP-d-apiose and UDP-d-xylose. An acetyl-protected phosphonate analogue of UDP-d-apiose was synthesized and used in an in situ HPLC assay to demonstrate for the first time the ability of AXS to interconvert the two reaction products. Density functional theory calculations provided insight into the energetics of this process and the apparent inability of AXS to catalyze the conversion of UDP-d-xylose to UDP-d-apiose. The data suggest that this observation is unlikely to be due to an unfavorable equilibrium but rather results from substrate inhibition by the most stable chair conformation of UDP-d-xylose. The detection of xylose cyclic phosphonate as the turnover product reveals significant new details about the AXS-catalyzed reaction and supports the proposed retroaldol-aldol mechanism of catalysis.

Original languageEnglish
Pages (from-to)13946-13949
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number34
DOIs
Publication statusPublished - 2012 Aug 29

Fingerprint

Uridine Diphosphate Xylose
Organophosphonates
Xylose
Uridine Diphosphate
Uridine Diphosphate Glucuronic Acid
Catalysis
Reaction products
Catalyst supports
High Pressure Liquid Chromatography
Glucuronic Acid
Density functional theory
Conformations
Assays
3-hydroxybutanal
UDPglucuronate decarboxylase
UDP-apiose
Acids
Substrates

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Analysis of UDP-D-apiose/UDP-D-xylose synthase-catalyzed conversion of UDP-D-apiose phosphonate to UDP-D-xylose phosphonate : Implications for a retroaldol-aldol mechanism. / Choi, Sei Hyun; Mansoorabadi, Steven O.; Liu, Yung Nan; Chien, Tun Cheng; Liu, Hung Wen.

In: Journal of the American Chemical Society, Vol. 134, No. 34, 29.08.2012, p. 13946-13949.

Research output: Contribution to journalArticle

@article{7e864dadaf8a4486a5ea026c2fc23f97,
title = "Analysis of UDP-D-apiose/UDP-D-xylose synthase-catalyzed conversion of UDP-D-apiose phosphonate to UDP-D-xylose phosphonate: Implications for a retroaldol-aldol mechanism",
abstract = "UDP-d-apiose/UDP-d-xylose synthase (AXS) catalyzes the conversion of UDP-d-glucuronic acid to UDP-d-apiose and UDP-d-xylose. An acetyl-protected phosphonate analogue of UDP-d-apiose was synthesized and used in an in situ HPLC assay to demonstrate for the first time the ability of AXS to interconvert the two reaction products. Density functional theory calculations provided insight into the energetics of this process and the apparent inability of AXS to catalyze the conversion of UDP-d-xylose to UDP-d-apiose. The data suggest that this observation is unlikely to be due to an unfavorable equilibrium but rather results from substrate inhibition by the most stable chair conformation of UDP-d-xylose. The detection of xylose cyclic phosphonate as the turnover product reveals significant new details about the AXS-catalyzed reaction and supports the proposed retroaldol-aldol mechanism of catalysis.",
author = "Choi, {Sei Hyun} and Mansoorabadi, {Steven O.} and Liu, {Yung Nan} and Chien, {Tun Cheng} and Liu, {Hung Wen}",
year = "2012",
month = "8",
day = "29",
doi = "10.1021/ja305322x",
language = "English",
volume = "134",
pages = "13946--13949",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "34",

}

TY - JOUR

T1 - Analysis of UDP-D-apiose/UDP-D-xylose synthase-catalyzed conversion of UDP-D-apiose phosphonate to UDP-D-xylose phosphonate

T2 - Implications for a retroaldol-aldol mechanism

AU - Choi, Sei Hyun

AU - Mansoorabadi, Steven O.

AU - Liu, Yung Nan

AU - Chien, Tun Cheng

AU - Liu, Hung Wen

PY - 2012/8/29

Y1 - 2012/8/29

N2 - UDP-d-apiose/UDP-d-xylose synthase (AXS) catalyzes the conversion of UDP-d-glucuronic acid to UDP-d-apiose and UDP-d-xylose. An acetyl-protected phosphonate analogue of UDP-d-apiose was synthesized and used in an in situ HPLC assay to demonstrate for the first time the ability of AXS to interconvert the two reaction products. Density functional theory calculations provided insight into the energetics of this process and the apparent inability of AXS to catalyze the conversion of UDP-d-xylose to UDP-d-apiose. The data suggest that this observation is unlikely to be due to an unfavorable equilibrium but rather results from substrate inhibition by the most stable chair conformation of UDP-d-xylose. The detection of xylose cyclic phosphonate as the turnover product reveals significant new details about the AXS-catalyzed reaction and supports the proposed retroaldol-aldol mechanism of catalysis.

AB - UDP-d-apiose/UDP-d-xylose synthase (AXS) catalyzes the conversion of UDP-d-glucuronic acid to UDP-d-apiose and UDP-d-xylose. An acetyl-protected phosphonate analogue of UDP-d-apiose was synthesized and used in an in situ HPLC assay to demonstrate for the first time the ability of AXS to interconvert the two reaction products. Density functional theory calculations provided insight into the energetics of this process and the apparent inability of AXS to catalyze the conversion of UDP-d-xylose to UDP-d-apiose. The data suggest that this observation is unlikely to be due to an unfavorable equilibrium but rather results from substrate inhibition by the most stable chair conformation of UDP-d-xylose. The detection of xylose cyclic phosphonate as the turnover product reveals significant new details about the AXS-catalyzed reaction and supports the proposed retroaldol-aldol mechanism of catalysis.

UR - http://www.scopus.com/inward/record.url?scp=84865639328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865639328&partnerID=8YFLogxK

U2 - 10.1021/ja305322x

DO - 10.1021/ja305322x

M3 - Article

C2 - 22830643

AN - SCOPUS:84865639328

VL - 134

SP - 13946

EP - 13949

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 34

ER -