So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic.Long, Tao; Qi, Xiaofeng; Hassan, Abdirahman; Liang, Qiren; De Brabander, Jef K.; Li, Xiaochun researched the compound: 3-Bromo-4-chloronitrobenzene( cas:16588-26-4 ).Safety of 3-Bromo-4-chloronitrobenzene.They published the article 《Structural basis for itraconazole-mediated NPC1 inhibition》 about this compound( cas:16588-26-4 ) in Nature Communications. Keywords: ovarian cell NPC1 itraconazole sterol sensing domain cholesterol. We’ll tell you more about this compound (cas:16588-26-4).
Niemann-Pick C1, a lysosomal protein of 13 transmembrane helixes and three lumenal domains, exports low-d.-lipoprotein-derived cholesterol from lysosomes. TMs 3-7 of NPC1 comprise the sterol-sensing domain. Previous studies suggest that mutation of the NPC1-SSD or the addition of the anti-fungal drug itraconazole abolishes NPC1 activity in cells. However, the itraconazole binding site and the mechanism of NPC1-mediated cholesterol transport remain unknown. Here, we report a cryo-EM structure of human NPC1 bound to itraconazole, which reveals how this binding site in the center of NPC1 blocks a putative lumenal tunnel linked to the SSD. Functional assays confirm that blocking this tunnel abolishes NPC1-mediated cholesterol egress. Intriguingly, the palmitate anchor of Hedgehog occupies a similar site in the homologous tunnel of Patched, suggesting a conserved mechanism for sterol transport in this family of proteins and establishing a central function of their SSDs.
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