Comparison of vibrational frequencies of critical bonds in ground-state complexes and in a vanadate-based transition-state analog complex of muscle phosphoglucomutase. Mechanistic implications

Hua Deng

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The symmetric stretching frequency of the PO bonds of the enzymic phosphate group in muscle phosphoglucomutase was measured via 16O/18O Raman difference spectroscopy. This frequency, and its shift on isotopic substitution, is characteristic of a dianionic phosphate ester. The PO stretching frequency is not detectably altered by the binding of the metal ion activators Mg2+, Zn2+, or Cd2+ nor by the subsequent binding of glucose phosphate. Hence, a binding-induced distortion/polarization of the enzymic phosphate group in the ground state, or enzyme-substrate complex, cannot serve as a rationale for the large value of kcat in the phosphoglucomutase reaction. By contrast, the stretching frequency of the VO bonds within a vanadate group bound at the same site in the transition-state analog complex involving glucose 1-phosphate 6-vanadate is much lower than for a normal dianionic vanadate. This low VO stretching frequency is best rationalized in terms of the extensive polarization of all three nonbridging oxygens of the vanadate ester dianion plus the formation of a weak, fifth bond to the vanadium atom. This distortion/polarization of the VO32- group depends on the metal ion activator, since it is largely abolished, and the involvement of the fifth ligand eliminated, by substitution of Li+ for Mg2+ at the metal activation site. To the extent that the vanadate-inhibitor complex mimics the transition state for the normal phosphoglucomutase reaction, as has been suggested [Ray, W. J., Jr., & Puvathingal, J. M. (1990) Biochemistry 29, 2790], the normal PO3- transfer is best described as a process with SN2-like or associative character and thus is quite different from the process by which model phosphate ester dianions normally react in aqueous solution.

Original languageEnglish (US)
Pages (from-to)12984-12992
Number of pages9
JournalBiochemistry®
Volume32
Issue number48
StatePublished - 1993
Externally publishedYes

Fingerprint

Phosphoglucomutase
Vanadates
Vibrational spectra
Electron transitions
Ground state
Muscle
Phosphates
Stretching
Muscles
Esters
Metals
Polarization
Metal ions
Substitution reactions
Ions
Vanadium
Biochemistry
Raman Spectrum Analysis
Chemical activation
Spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{06d6ca7bc4164eb68c0aa31e517fce30,
title = "Comparison of vibrational frequencies of critical bonds in ground-state complexes and in a vanadate-based transition-state analog complex of muscle phosphoglucomutase. Mechanistic implications",
abstract = "The symmetric stretching frequency of the PO bonds of the enzymic phosphate group in muscle phosphoglucomutase was measured via 16O/18O Raman difference spectroscopy. This frequency, and its shift on isotopic substitution, is characteristic of a dianionic phosphate ester. The PO stretching frequency is not detectably altered by the binding of the metal ion activators Mg2+, Zn2+, or Cd2+ nor by the subsequent binding of glucose phosphate. Hence, a binding-induced distortion/polarization of the enzymic phosphate group in the ground state, or enzyme-substrate complex, cannot serve as a rationale for the large value of kcat in the phosphoglucomutase reaction. By contrast, the stretching frequency of the VO bonds within a vanadate group bound at the same site in the transition-state analog complex involving glucose 1-phosphate 6-vanadate is much lower than for a normal dianionic vanadate. This low VO stretching frequency is best rationalized in terms of the extensive polarization of all three nonbridging oxygens of the vanadate ester dianion plus the formation of a weak, fifth bond to the vanadium atom. This distortion/polarization of the VO32- group depends on the metal ion activator, since it is largely abolished, and the involvement of the fifth ligand eliminated, by substitution of Li+ for Mg2+ at the metal activation site. To the extent that the vanadate-inhibitor complex mimics the transition state for the normal phosphoglucomutase reaction, as has been suggested [Ray, W. J., Jr., & Puvathingal, J. M. (1990) Biochemistry 29, 2790], the normal PO3- transfer is best described as a process with SN2-like or associative character and thus is quite different from the process by which model phosphate ester dianions normally react in aqueous solution.",
author = "Hua Deng",
year = "1993",
language = "English (US)",
volume = "32",
pages = "12984--12992",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "48",

}

TY - JOUR

T1 - Comparison of vibrational frequencies of critical bonds in ground-state complexes and in a vanadate-based transition-state analog complex of muscle phosphoglucomutase. Mechanistic implications

AU - Deng, Hua

PY - 1993

Y1 - 1993

N2 - The symmetric stretching frequency of the PO bonds of the enzymic phosphate group in muscle phosphoglucomutase was measured via 16O/18O Raman difference spectroscopy. This frequency, and its shift on isotopic substitution, is characteristic of a dianionic phosphate ester. The PO stretching frequency is not detectably altered by the binding of the metal ion activators Mg2+, Zn2+, or Cd2+ nor by the subsequent binding of glucose phosphate. Hence, a binding-induced distortion/polarization of the enzymic phosphate group in the ground state, or enzyme-substrate complex, cannot serve as a rationale for the large value of kcat in the phosphoglucomutase reaction. By contrast, the stretching frequency of the VO bonds within a vanadate group bound at the same site in the transition-state analog complex involving glucose 1-phosphate 6-vanadate is much lower than for a normal dianionic vanadate. This low VO stretching frequency is best rationalized in terms of the extensive polarization of all three nonbridging oxygens of the vanadate ester dianion plus the formation of a weak, fifth bond to the vanadium atom. This distortion/polarization of the VO32- group depends on the metal ion activator, since it is largely abolished, and the involvement of the fifth ligand eliminated, by substitution of Li+ for Mg2+ at the metal activation site. To the extent that the vanadate-inhibitor complex mimics the transition state for the normal phosphoglucomutase reaction, as has been suggested [Ray, W. J., Jr., & Puvathingal, J. M. (1990) Biochemistry 29, 2790], the normal PO3- transfer is best described as a process with SN2-like or associative character and thus is quite different from the process by which model phosphate ester dianions normally react in aqueous solution.

AB - The symmetric stretching frequency of the PO bonds of the enzymic phosphate group in muscle phosphoglucomutase was measured via 16O/18O Raman difference spectroscopy. This frequency, and its shift on isotopic substitution, is characteristic of a dianionic phosphate ester. The PO stretching frequency is not detectably altered by the binding of the metal ion activators Mg2+, Zn2+, or Cd2+ nor by the subsequent binding of glucose phosphate. Hence, a binding-induced distortion/polarization of the enzymic phosphate group in the ground state, or enzyme-substrate complex, cannot serve as a rationale for the large value of kcat in the phosphoglucomutase reaction. By contrast, the stretching frequency of the VO bonds within a vanadate group bound at the same site in the transition-state analog complex involving glucose 1-phosphate 6-vanadate is much lower than for a normal dianionic vanadate. This low VO stretching frequency is best rationalized in terms of the extensive polarization of all three nonbridging oxygens of the vanadate ester dianion plus the formation of a weak, fifth bond to the vanadium atom. This distortion/polarization of the VO32- group depends on the metal ion activator, since it is largely abolished, and the involvement of the fifth ligand eliminated, by substitution of Li+ for Mg2+ at the metal activation site. To the extent that the vanadate-inhibitor complex mimics the transition state for the normal phosphoglucomutase reaction, as has been suggested [Ray, W. J., Jr., & Puvathingal, J. M. (1990) Biochemistry 29, 2790], the normal PO3- transfer is best described as a process with SN2-like or associative character and thus is quite different from the process by which model phosphate ester dianions normally react in aqueous solution.

UR - http://www.scopus.com/inward/record.url?scp=0027764334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027764334&partnerID=8YFLogxK

M3 - Article

C2 - 8241152

AN - SCOPUS:0027764334

VL - 32

SP - 12984

EP - 12992

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 48

ER -