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2001 | 48 | 4 | 885-892

Article title

Comparison of binding interactions of dibromoflavonoids with transthyretin.

Content

Title variants

Languages of publication

EN

Abstracts

EN
The crystal structure of rat transthyretin (rTTR) complex with the dibromoflavone EMD21388 was determined to 2.3 Å resolution and refined to R = 0.203 and Rfree = 0.288. Two different orientations of EMD21388, which differ in the channel penetration by 1.6 Å, were found in the A/C binding site of rTTR. The single ligand position observed in the B/D site is intermediate between the two positions found in the A/C site. The position of the dibromoflavone in the B/D site is similar to that reported for dibromoaurone in human TTR. The bromine atoms of EMD21388 form strong interactions in the P3 and P3' pockets of rTTR. Due to the different molecular architectures of both ligands, dibromoflavone forms only one interaction with Lys-15 near the channel entrance, while direct interactions with the pair of Lys-15 were reported for dibromoaurone. The C3* methyl group of EMD21388 mediates the bridging interactions between two TTR subunits in the P2 pockets. The interactions of the O2* hydroxyl group of dibromoaurone with the Thr-119 side chain in the P3 pockets are not matched by similar interactions in EMD21388. Both these alternative interactions can explain the competitive binding of 3',5'-dibromoflavonoids to transthyretin.

Year

Volume

48

Issue

4

Pages

885-892

Physical description

Dates

published
2001
received
2001-10-16
accepted
2001-12-4

Contributors

  • Institute of Chemistry, Nicolaus Copernicus University, Toruń, Poland
author
  • Hauptman-Woodward Medical Research Institute, Inc., Buffalo, U.S.A.
  • Institute of Chemistry, Nicolaus Copernicus University, Toruń, Poland

References

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Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.bwnjournal-article-abpv48i4p885kz
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