Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors

Mirsada Causevic; C. Roland Wolf; Colin N.A. Palmer

doi:10.1016/S0014-5793(99)01618-X

Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors

Mirsada Causevic, C. Roland Wolf, Colin N.A. Palmer (Lead / Corresponding author)

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

9 Citations (Scopus)

Abstract

Mutation of glutamic acid 282 of PPARα to glycine has been shown to result in an increased EC₅₀ for a wide variety of PPAR activating compounds. This has suggested that mutant receptor has a reduced ability to bind ligand. In this study we show that this mutation reduces the affinity of mPPARα and hPPARγ for the fluorescent fatty acid, cis-parinaric acid and that the mutant hPPARγ protein has a reduced affinity for the radiolabelled compound, SB236636. These data confirm the role of this glutamic acid in ligand binding and support recent crystal structure observations regarding a proposed novel mode of ligand entry into the PPAR ligand binding cavities.

Original language	English
Pages (from-to)	205-210
Number of pages	6
Journal	FEBS Letters
Volume	463
Issue number	3
DOIs	https://doi.org/10.1016/S0014-5793(99)01618-X
Publication status	Published - 17 Dec 1999

Keywords

Diabetes
Fatty acid
Fluorescence
Nuclear receptor
Peroxisome proliferator
Thiazolidinedione

ASJC Scopus subject areas

Structural Biology
Biophysics
Biochemistry
Molecular Biology
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0014-5793(99)01618-X

Cite this

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abstract = "Mutation of glutamic acid 282 of PPARα to glycine has been shown to result in an increased EC50 for a wide variety of PPAR activating compounds. This has suggested that mutant receptor has a reduced ability to bind ligand. In this study we show that this mutation reduces the affinity of mPPARα and hPPARγ for the fluorescent fatty acid, cis-parinaric acid and that the mutant hPPARγ protein has a reduced affinity for the radiolabelled compound, SB236636. These data confirm the role of this glutamic acid in ligand binding and support recent crystal structure observations regarding a proposed novel mode of ligand entry into the PPAR ligand binding cavities.",

keywords = "Diabetes, Fatty acid, Fluorescence, Nuclear receptor, Peroxisome proliferator, Thiazolidinedione",

author = "Mirsada Causevic and Wolf, \{C. Roland\} and Palmer, \{Colin N.A.\}",

year = "1999",

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language = "English",

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pages = "205--210",

journal = "FEBS Letters",

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T1 - Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors

AU - Causevic, Mirsada

AU - Wolf, C. Roland

AU - Palmer, Colin N.A.

PY - 1999/12/17

Y1 - 1999/12/17

N2 - Mutation of glutamic acid 282 of PPARα to glycine has been shown to result in an increased EC50 for a wide variety of PPAR activating compounds. This has suggested that mutant receptor has a reduced ability to bind ligand. In this study we show that this mutation reduces the affinity of mPPARα and hPPARγ for the fluorescent fatty acid, cis-parinaric acid and that the mutant hPPARγ protein has a reduced affinity for the radiolabelled compound, SB236636. These data confirm the role of this glutamic acid in ligand binding and support recent crystal structure observations regarding a proposed novel mode of ligand entry into the PPAR ligand binding cavities.

AB - Mutation of glutamic acid 282 of PPARα to glycine has been shown to result in an increased EC50 for a wide variety of PPAR activating compounds. This has suggested that mutant receptor has a reduced ability to bind ligand. In this study we show that this mutation reduces the affinity of mPPARα and hPPARγ for the fluorescent fatty acid, cis-parinaric acid and that the mutant hPPARγ protein has a reduced affinity for the radiolabelled compound, SB236636. These data confirm the role of this glutamic acid in ligand binding and support recent crystal structure observations regarding a proposed novel mode of ligand entry into the PPAR ligand binding cavities.

KW - Diabetes

KW - Fatty acid

KW - Fluorescence

KW - Nuclear receptor

KW - Peroxisome proliferator

KW - Thiazolidinedione

UR - https://www.scopus.com/pages/publications/0033437183

U2 - 10.1016/S0014-5793(99)01618-X

DO - 10.1016/S0014-5793(99)01618-X

M3 - Article

C2 - 10606722

AN - SCOPUS:0033437183

SN - 0014-5793

VL - 463

SP - 205

EP - 210

JO - FEBS Letters

JF - FEBS Letters

IS - 3

ER -

Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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