1KGJ

Rat transthyretin (also called prealbumin) complex with 3',5'-dibromoflavone (EMD21388)

Summary for 1KGJ

• Entry DOI: 10.2210/pdb1kgj/pdb
• Related: 1GKE 1KED 1KGI 2ROX
• Descriptor: TRANSTHYRETIN, 6,4'-DIHYDROXY-3-METHYL-3',5'-DIBROMOFLAVONE (3 entities in total)
• Functional Keywords: prealbumin, transport, dibromoflavone, aurone, thyroid hormone, transport protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Secreted: P02767
• Total number of polymer chains: 4
• Total formula weight: 55308.70

Authors

Wojtczak, A.,Neumann, P.,Muziol, T.,Cody, V.,Luft, J.R.,Pangborn, W. (deposition date: 2001-11-27, release date: 2002-11-27, Last modification date: 2023-08-16)

Primary citation

Muziol, T.,Cody, V.,Wojtczak, A.
Comparison of binding interactions of dibromoflavonoids with transthyretin.
Acta Biochim.Pol., 48:885-892, 2001

PubMed Abstract: 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 penetration by 1.6 A, were found in the A/C binding site of rTTR. The single ligand position observed in the BID 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.

PubMed: 11995999

Experimental method

X-RAY DIFFRACTION (2.3 Å)