Troglitazone, an euglycemic antidiabetic drug

Vyas, K.; Sivalakshmidevi, A.; Prabhakar, C.; Reddy, G. Om

doi:10.1107/s010827019801467x

Cited by 9 publications

(7 citation statements)

References 1 publication

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“…The size, shape and location of the region corresponded well to the naphthalene ring system of ANS as bound to FABP4 in the PDB structure 2ANS. 43 The hydroxy-tetramethyl chroman ring system of troglitazone is similar in shape to naphthalene, only somewhat larger and possessing a puckered six-membered ring. When placed within the observed density, the methoxy-linked benzyl group can be made to extend toward the same pocket occupied by the aniline portion of ANS.…”

Section: Crystallographymentioning

confidence: 99%

Structural Basis for Activation of Fatty Acid-binding Protein 4

Gillilan

Ayers

Noy

2007

Journal of Molecular Biology

151

153

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Fatty acid-binding protein 4 (FABP4) delivers ligands from the cytosol to the nuclear receptor PPARgamma in the nucleus, thereby enhancing the transcriptional activity of the receptor. Notably, FABP4 binds multiple ligands with a similar affinity but its nuclear translocation is activated only by specific compounds. To gain insight into the structural features that underlie the ligand-specificity in activation of the nuclear import of FABP4, we solved the crystal structures of the protein complexed with two compounds that induce its nuclear translocation, and compared these to the apo-protein and to FABP4 structures bound to non-activating ligands. Examination of these structures indicates that activation coincides with closure of a portal loop phenylalanine side-chain, contraction of the binding pocket, a subtle shift in a helical domain containing the nuclear localization signal of the protein, and a resultant change in oligomeric state that exposes the nuclear localization signal to the solution. Comparisons of backbone displacements induced by activating ligands with a measure of mobility derived from translation, libration, screw (TLS) refinement, and with a composite of slowest normal modes of the apo state suggest that the helical motion associated with the activation of the protein is part of the repertoire of the equilibrium motions of the apo-protein, i.e. that ligand binding does not induce the activated configuration but serves to stabilize it. Nuclear import of FABP4 can thus be understood in terms of the pre-existing equilibrium hypothesis of ligand binding.

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Section: Crystallographymentioning

confidence: 99%

Structural Basis for Activation of Fatty Acid-binding Protein 4

Gillilan

Ayers

Noy

2007

Journal of Molecular Biology

151

153

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“…Both diastereomer molecules were disordered at the asymmetric C(5) atom in the crystal packing. The conformation of the (±)-(2R*,5S*) isomer in the dihydrate was similar to that of the pure (±)-(2R*,5S*) isomer crystal, 1 conformation from the pure (±)-(2R*,5R*) isomer crystal. 2 In the mixed crystal, thiazolidine rings were in the envelope conformation; the C(5a) and the C(5b) atoms were displaced by 0.366(5)Å and -0.598 (9) …”

mentioning

confidence: 64%

Crystal Structure of an Antidiabetic Agent, (±)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmethoxy)benzyl]-2,4-dioxothiazollidine, Troglitazone Dihydrate

2001

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“…The crystal structures of the RS/SR form and the monohydrate of the RR/SS form have been already studied [14,15]. Troglitazone has hydrophilic function only at the both edges of its molecule (6 -OH and thiazolidinedione), and the other groups are hydrophobic.…”

Section: Ssnmr Spectroscopy Of Troglitazone Diastereomersmentioning

confidence: 99%