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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Diabetes
Fatty acid
Fluorescence
Nuclear receptor
Peroxisome proliferator
Thiazolidinedione

ASJC Scopus subject areas

Structural Biology
Biophysics
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(99)01618-X

Cite this

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

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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doi = "10.1016/S0014-5793(99)01618-X",

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

UN SDGs

Keywords

ASJC Scopus subject areas

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