《Exploring the quinone/inhibitor-binding pocket in mitochondrial respiratory complex I by chemical biology approaches》 was written by Uno, Shinpei; Kimura, Hironori; Murai, Masatoshi; Miyoshi, Hideto. Application of 13325-10-5This research focused onubiquinone analog respiratory complex I quinone binding pocket inhibitor; Complex I; NADH–quinone oxidoreductase; amilorides; bioenergetics; chemical biology; enzyme inhibitor; mitochondria; photoaffinity labeling; ubiquinone. The article conveys some information:
NADH-quinone oxidoreductase (respiratory complex I) couples NADH-to-quinone electron transfer to the translocation of protons across the membrane. Even though the architecture of the quinone-access channel in the enzyme has been modeled by X-ray crystallog. and cryo-EM, conflicting findings raise the question whether the models fully reflect physiol. relevant states present throughout the catalytic cycle. To gain further insights into the structural features of the binding pocket for quinone/inhibitor, we performed chem. biol. experiments using bovine heart sub-mitochondrial particles. We synthesized ubiquinones (UQs) that are oversized ,(i.e., SF-UQs) or lipid-like (i.e., PC-UQs) and are highly unlikely to enter and transit the predicted narrow channel. We found that SF-UQs and PC-UQs can be catalytically reduced by complex I, albeit only at moderate or low rates. Moreover, quinone-site inhibitors completely blocked the catalytic reduction and the membrane potential formation coupled to this reduction Photoaffinity-labeling experiments revealed that amiloride-type inhibitors bind to the interfacial domain of multiple core subunits (49 kDa, ND1, and PSST) and the 39-kDa supernumerary subunit, although the latter does not make up the channel cavity in the current models. The binding of amilorides to the multiple target subunits was remarkably suppressed by other quinone-site inhibitors and SF-UQs. Taken together, the present results are difficult to reconcile with the current channel models. On the basis of comprehensive interpretations of the present results and of previous findings, we discuss the physiol. relevance of these models. In the experimental materials used by the author, we found 4-Aminobutan-1-ol(cas: 13325-10-5Application of 13325-10-5)
4-Aminobutan-1-ol(cas: 13325-10-5) is used in the synthesis of NSAIDs with anti-inflammatory properties. Also used in the synthesis of polyamine transport ligands with specificity against human cancers allowing easy access to specific cancer cells.Application of 13325-10-5
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