L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase: X-Ray/Neutron crystallographic and molecular simulation study

Paul Langan; Amandeep K. Sangha; Troy Wymore; Jerry M. Parks; Zamin Koo Yang; B. Leif Hanson; Zoe Fisher; Sax A. Mason; Matthew P. Blakeley; V. Trevor Forsyth; Jenny P. Glusker; Horace L. Carrell; Jeremy C. Smith; David A. Keen; David E. Graham; Andrey Kovalevsky

doi:10.1016/j.str.2014.07.002

L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase: X-Ray/Neutron crystallographic and molecular simulation study

Paul Langan, Amandeep K. Sangha, Troy Wymore, Jerry M. Parks, Zamin Koo Yang, B. Leif Hanson, Zoe Fisher, Sax A. Mason, Matthew P. Blakeley, V. Trevor Forsyth, Jenny P. Glusker, Horace L. Carrell, Jeremy C. Smith, David A. Keen, David E. Graham, Andrey Kovalevsky

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of some monosaccharides into their C2-epimers. We present X-ray and neutron crystallographic studies to locate H and D atoms during the respective isomerization and epimerization of L-arabinose to L-ribulose and L-ribose, respectively. Neutron structures in complex with cyclic and linear L-arabinose have demonstrated that the mechanism of ring-opening is the same as for the reaction with D-xylose. Structural evidence and QM/MM calculations show that in the reactive Michaelis complex L-arabinose is distorted to the high-energy ⁵S₁ conformation; this may explain the apparent high K_M for this sugar. MD-FEP simulations indicate that amino acid substitutions in a hydrophobic pocket near C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found in furanose forms when bound to XI. We propose that these complexes containing Ni²⁺ cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism.

Original language	English
Pages (from-to)	1287-1300
Number of pages	14
Journal	Structure
Volume	22
Issue number	9
DOIs	https://doi.org/10.1016/j.str.2014.07.002
State	Published - Sep 2 2014

Funding

The PCS is funded by the Office of Biological and Environmental Research of the Department of Energy . The PCS is located at the Lujan Center at Los Alamos Neutron Science Center, funded by the DOE Office of Basic Energy Sciences . This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the US Department of Energy under contract no. DE-AC02-05CH11231 . The D19 diffractometer was built as part of a collaboration between Durham University, Keele University, Bath University, and ILL ( EPSRC grant GR/R47950/01 ). We gratefully acknowledge the help of John Archer, John Allibon, and the efforts of the ILL detector group. P.L., A.K.S., T.W., J.M.P., Z.K.Y., D.E.G., and A.K. were partly supported by the DOE Office of Biological and Environmental Research . P.L. was partly supported by an NIH-NIGMS funded consortium between ORNL and LBNL to develop computational tools for neutron protein crystallography.

Access to Document

10.1016/j.str.2014.07.002

Cite this

Langan, P., Sangha, A. K., Wymore, T., Parks, J. M., Yang, Z. K., Hanson, B. L., Fisher, Z., Mason, S. A., Blakeley, M. P., Forsyth, V. T., Glusker, J. P., Carrell, H. L., Smith, J. C., Keen, D. A., Graham, D. E., & Kovalevsky, A. (2014). L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase: X-Ray/Neutron crystallographic and molecular simulation study. Structure, 22(9), 1287-1300. https://doi.org/10.1016/j.str.2014.07.002

@article{0ed0bb4c58ad4042b8a1ed267ed2b437,

title = "L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase: X-Ray/Neutron crystallographic and molecular simulation study",

abstract = "D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of some monosaccharides into their C2-epimers. We present X-ray and neutron crystallographic studies to locate H and D atoms during the respective isomerization and epimerization of L-arabinose to L-ribulose and L-ribose, respectively. Neutron structures in complex with cyclic and linear L-arabinose have demonstrated that the mechanism of ring-opening is the same as for the reaction with D-xylose. Structural evidence and QM/MM calculations show that in the reactive Michaelis complex L-arabinose is distorted to the high-energy 5S1 conformation; this may explain the apparent high KM for this sugar. MD-FEP simulations indicate that amino acid substitutions in a hydrophobic pocket near C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found in furanose forms when bound to XI. We propose that these complexes containing Ni2+ cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism.",

author = "Paul Langan and Sangha, {Amandeep K.} and Troy Wymore and Parks, {Jerry M.} and Yang, {Zamin Koo} and Hanson, {B. Leif} and Zoe Fisher and Mason, {Sax A.} and Blakeley, {Matthew P.} and Forsyth, {V. Trevor} and Glusker, {Jenny P.} and Carrell, {Horace L.} and Smith, {Jeremy C.} and Keen, {David A.} and Graham, {David E.} and Andrey Kovalevsky",

year = "2014",

month = sep,

day = "2",

doi = "10.1016/j.str.2014.07.002",

language = "English",

volume = "22",

pages = "1287--1300",

journal = "Structure",

issn = "0969-2126",

publisher = "Elsevier",

number = "9",

}

Langan, P, Sangha, AK, Wymore, T, Parks, JM, Yang, ZK, Hanson, BL, Fisher, Z, Mason, SA, Blakeley, MP, Forsyth, VT, Glusker, JP, Carrell, HL, Smith, JC, Keen, DA, Graham, DE & Kovalevsky, A 2014, 'L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase: X-Ray/Neutron crystallographic and molecular simulation study', Structure, vol. 22, no. 9, pp. 1287-1300. https://doi.org/10.1016/j.str.2014.07.002

TY - JOUR

T1 - L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase

T2 - X-Ray/Neutron crystallographic and molecular simulation study

AU - Langan, Paul

AU - Sangha, Amandeep K.

AU - Wymore, Troy

AU - Parks, Jerry M.

AU - Yang, Zamin Koo

AU - Hanson, B. Leif

AU - Fisher, Zoe

AU - Mason, Sax A.

AU - Blakeley, Matthew P.

AU - Forsyth, V. Trevor

AU - Glusker, Jenny P.

AU - Carrell, Horace L.

AU - Smith, Jeremy C.

AU - Keen, David A.

AU - Graham, David E.

AU - Kovalevsky, Andrey

PY - 2014/9/2

Y1 - 2014/9/2

N2 - D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of some monosaccharides into their C2-epimers. We present X-ray and neutron crystallographic studies to locate H and D atoms during the respective isomerization and epimerization of L-arabinose to L-ribulose and L-ribose, respectively. Neutron structures in complex with cyclic and linear L-arabinose have demonstrated that the mechanism of ring-opening is the same as for the reaction with D-xylose. Structural evidence and QM/MM calculations show that in the reactive Michaelis complex L-arabinose is distorted to the high-energy 5S1 conformation; this may explain the apparent high KM for this sugar. MD-FEP simulations indicate that amino acid substitutions in a hydrophobic pocket near C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found in furanose forms when bound to XI. We propose that these complexes containing Ni2+ cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism.

AB - D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of some monosaccharides into their C2-epimers. We present X-ray and neutron crystallographic studies to locate H and D atoms during the respective isomerization and epimerization of L-arabinose to L-ribulose and L-ribose, respectively. Neutron structures in complex with cyclic and linear L-arabinose have demonstrated that the mechanism of ring-opening is the same as for the reaction with D-xylose. Structural evidence and QM/MM calculations show that in the reactive Michaelis complex L-arabinose is distorted to the high-energy 5S1 conformation; this may explain the apparent high KM for this sugar. MD-FEP simulations indicate that amino acid substitutions in a hydrophobic pocket near C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found in furanose forms when bound to XI. We propose that these complexes containing Ni2+ cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism.

UR - http://www.scopus.com/inward/record.url?scp=84930065049&partnerID=8YFLogxK

U2 - 10.1016/j.str.2014.07.002

DO - 10.1016/j.str.2014.07.002

M3 - Article

C2 - 25132082

AN - SCOPUS:84930065049

SN - 0969-2126

VL - 22

SP - 1287

EP - 1300

JO - Structure

JF - Structure

IS - 9

ER -

L-Arabinose binding, isomerization, and epimerization by D-Xylose isomerase: X-Ray/Neutron crystallographic and molecular simulation study

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this