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2001 | 48 | 4 |

Tytuł artykułu

Comparison of binding interactions of dibromoflavonoids with transthyretin

Warianty tytułu

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.

Wydawca

-

Rocznik

Tom

48

Numer

4

Opis fizyczny

p.885-892,fig.

Twórcy

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

Bibliografia

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Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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