NMR studies of fluororetinol analogs complexed to two homologous rat cellular retinol-binding proteins

Ding Rong; Allen J. Lovey; Michael Rosenberger; D. Andréd'Avignon; Ellen Li

doi:10.1016/0167-4838(94)90170-8

NMR studies of fluororetinol analogs complexed to two homologous rat cellular retinol-binding proteins

Ding Rong, Allen J. Lovey, Michael Rosenberger, D. Andréd'Avignon, Ellen Li

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Abstract

Comparative ¹⁹F-NMR studies of fluororetinol analogs with rat cellular retinol binding protein II (CRBP II) and rat cellular retinol-binding protein (CRBP) were performed to probe differences in the binding interactions of these two homologous proteins. Line shape analyses of ¹⁹F-NMR spectra of (E,E,Z,E)-6-fluoro-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetren-1-ol (ligand 1), (E,E,Z,E)-6-fluoro-9-(2,2′dimethyl-6-ethylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren-1-ol (ligand 2), (E,Z,E,E)-5-fluoro-9-(2,2′-dimethyl-6-methylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren-l-ol (ligand 3), when complexed with CRBP II at temperatures ranging from 0-45°C, revealed that the ¹⁹F resonances corresponding to the bound ligand were in slow chemical exchange between two resonance frequencies. This was further supported by a 2D-NOESY exchange experiment. The k_ex at 25°C was estimated from spectral simulation and fitting analyses to be 887 s^±1, 1010 s^±1and 771 s^±1 for CRBP II complexed 1, 2, and 3, respectively. In contrast, only a single absorption was observed for bound ligands complexed with rat CRBP over this temperature range, suggesting that the conformational dynamics of retinol binding are differeut for these two closely homologous proteins.

Original language	English (US)
Pages (from-to)	136-144
Number of pages	9
Journal	Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume	1208
Issue number	1
DOIs	https://doi.org/10.1016/0167-4838(94)90170-8
State	Published - Sep 21 1994
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants DK40172 and DK45755. NMR spectra were collected at the Washington University High Resolution NMR Service Facility which is funded in part through a NIH Biomedical Research Support Shared Instrument Grant LRR02004 and RR05018). E. Li is a recipient on an NIH RCDA (DK02072). We wish to thank Dr. Ira Ropson for helpful discussions on the DNMR5 program.

Keywords

Cellular retinol binding protein
Conformation
Dynamics
Retinol

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title = "NMR studies of fluororetinol analogs complexed to two homologous rat cellular retinol-binding proteins",

abstract = "Comparative 19F-NMR studies of fluororetinol analogs with rat cellular retinol binding protein II (CRBP II) and rat cellular retinol-binding protein (CRBP) were performed to probe differences in the binding interactions of these two homologous proteins. Line shape analyses of 19F-NMR spectra of (E,E,Z,E)-6-fluoro-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetren-1-ol (ligand 1), (E,E,Z,E)-6-fluoro-9-(2,2′dimethyl-6-ethylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren-1-ol (ligand 2), (E,Z,E,E)-5-fluoro-9-(2,2′-dimethyl-6-methylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren-l-ol (ligand 3), when complexed with CRBP II at temperatures ranging from 0-45°C, revealed that the 19F resonances corresponding to the bound ligand were in slow chemical exchange between two resonance frequencies. This was further supported by a 2D-NOESY exchange experiment. The kex at 25°C was estimated from spectral simulation and fitting analyses to be 887 s±1, 1010 s±1and 771 s±1 for CRBP II complexed 1, 2, and 3, respectively. In contrast, only a single absorption was observed for bound ligands complexed with rat CRBP over this temperature range, suggesting that the conformational dynamics of retinol binding are differeut for these two closely homologous proteins.",

keywords = "Cellular retinol binding protein, Conformation, Dynamics, Retinol",

author = "Ding Rong and Lovey, {Allen J.} and Michael Rosenberger and D. Andr{\'e}d'Avignon and Ellen Li",

note = "Funding Information: This work was supported by National Institutes of Health grants DK40172 and DK45755. NMR spectra were collected at the Washington University High Resolution NMR Service Facility which is funded in part through a NIH Biomedical Research Support Shared Instrument Grant LRR02004 and RR05018). E. Li is a recipient on an NIH RCDA (DK02072). We wish to thank Dr. Ira Ropson for helpful discussions on the DNMR5 program.",

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AU - Li, Ellen

N1 - Funding Information: This work was supported by National Institutes of Health grants DK40172 and DK45755. NMR spectra were collected at the Washington University High Resolution NMR Service Facility which is funded in part through a NIH Biomedical Research Support Shared Instrument Grant LRR02004 and RR05018). E. Li is a recipient on an NIH RCDA (DK02072). We wish to thank Dr. Ira Ropson for helpful discussions on the DNMR5 program.

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N2 - Comparative 19F-NMR studies of fluororetinol analogs with rat cellular retinol binding protein II (CRBP II) and rat cellular retinol-binding protein (CRBP) were performed to probe differences in the binding interactions of these two homologous proteins. Line shape analyses of 19F-NMR spectra of (E,E,Z,E)-6-fluoro-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetren-1-ol (ligand 1), (E,E,Z,E)-6-fluoro-9-(2,2′dimethyl-6-ethylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren-1-ol (ligand 2), (E,Z,E,E)-5-fluoro-9-(2,2′-dimethyl-6-methylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren-l-ol (ligand 3), when complexed with CRBP II at temperatures ranging from 0-45°C, revealed that the 19F resonances corresponding to the bound ligand were in slow chemical exchange between two resonance frequencies. This was further supported by a 2D-NOESY exchange experiment. The kex at 25°C was estimated from spectral simulation and fitting analyses to be 887 s±1, 1010 s±1and 771 s±1 for CRBP II complexed 1, 2, and 3, respectively. In contrast, only a single absorption was observed for bound ligands complexed with rat CRBP over this temperature range, suggesting that the conformational dynamics of retinol binding are differeut for these two closely homologous proteins.

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NMR studies of fluororetinol analogs complexed to two homologous rat cellular retinol-binding proteins

Abstract

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Keywords

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