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Protein and ligand adaptation in a retinoic acid binding protein
Author(s) -
Pattanayek Rekha,
Newcomer Marcia E.
Publication year - 1999
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.8.10.2027
Subject(s) - retinoic acid , chemistry , ligand (biochemistry) , retinoic acid receptor , stereochemistry , retinoid x receptor gamma , biochemistry , protein structure , retinoic acid inducible orphan g protein coupled receptor , receptor , gene
Abstract A retinoic acid binding protein isolated from the lumen of the rat epididymis (ERABP) is a member of the lipocalin superfamily. ERABP binds both the all‐trans and 9‐cis isomers of retinoic acid, as well as the synthetic retinoid (E)‐4‐[2‐(5,6,7,8)‐tetrahydro‐5,5,8,8‐tetramethyl‐2 napthalenyl‐1 propenyl]‐benzoic acid (TTNPB), a structural analog of all‐trans retinoic acid. The structure of ERABP with a mixture of all‐trans and 9‐cis retinoic acid has previously been reported. To elucidate any structural differences in the protein when bound to the all‐trans and 9‐cis isomers, the structures of all‐trans retinoic acid‐ERABP and 9‐cis retinoic acid ERABP were determined. Our results indicate that the all‐trans isomer of retinoic acid adopts an 8‐cis structure in the binding cavity with no concomitant conformational change in the protein. The structure of TTNPB‐ERABP is also reported herein. To accommodate this all‐trans analog, which cannot readily adopt a cis‐like structure, alternative positioning of critical binding site side chains is required. Consequently, both protein and ligand adaption are observed in the formation of the various holo‐proteins.