Comparison of binding interactions of dibromoflavonoids with transthyretin

• Autorzy: Muziol T. , Cody V. , Wojtczak A.
• Języki publikacji: EN

Abstrakty

EN

The crystal structure of rat transthyretin (rTTR) complex with the dibromoflavone EMD21388 was determined to 2.3 A resolution and refined to R = 0.203 and Rfree = 0.288. Two different orientations of EMD21388, which differ in the channel penetra tion by 1.6 A, 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.

Słowa kluczowe

EN

flavonoids; transthyretin; dibromoflavonoids; free radical; flavone; crystal structure; binding interaction; vegetable; bromine atom; rat; fruit

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2001
• Tom: 48
• Numer: 4
• Opis fizyczny: p.885-892,fig.

Twórcy

autor

Muziol T.

• Nicolaus Copernicus University, Gagarina 7, 87-100 Torun, Poland

autor

Cody V.

autor

Wojtczak A.

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