Masuya, Takahiro published the artcilePinpoint Dual Chemical Cross-Linking Explores the Structural Dynamics of the Ubiquinone Reaction Site in Mitochondrial Complex I, Recommanded Product: Dbco-maleimide, the publication is Biochemistry (2021), 60(10), 813-824, database is CAplus and MEDLINE.
The ubiquinone reduction step in NADH-ubiquinone oxidoreductase (complex I) is the key to triggering proton translocation in its membrane part. Although the existence of a long and narrow quinone-access channel was identified, it remains debatable whether the channel model can account for binding of various ligands (ubiquinones and inhibitors) to the enzyme. The authors previously proposed that the matrix-side interfacial region of the 49 kDa, ND1, PSST, and 39 kDa subunits, which is covered by a loop connecting transmembrane helixes (TMHs) 1 and 2 of ND3, may be the area for entry of some bulky ligands into the quinone reaction cavity. However, this proposition lacks direct evidence that the cavity is accessible from the putative matrix-side region, which allows ligands to pass. To address this, the authors examined whether Cys39 of ND3 and Asp160 of 49 kDa can be specifically crosslinked by bifunctional crosslinkers (tetrazine-maleimide hybrid, named TMBC). On the basis of the structural models of complex I, such dual crosslinking is unexpected because ND3 Cys39 and 49 kDa Asp160 are located on the TMH1-2 loop and deep inside the channel, resp., and hence, they are phys. separated by peptide chains forming the channel wall. However, three TMBCs with different spacer lengths did crosslink the two residues, giving new crosslinked ND3/49 kDa subunits. Chem. modification of either ND3 Cys39 or 49 kDa Asp160 blocked the dual crosslinking, ensuring the specificity of the crosslinking. Altogether, this study provides direct evidence that the quinone reaction cavity is indeed accessible from the proposed matrix-side region covered by the ND3 TMH1-2 loop.
Biochemistry published new progress about 1395786-30-7. 1395786-30-7 belongs to catalysis-chemistry, auxiliary class Inhibitor, name is Dbco-maleimide, and the molecular formula is C25H21N3O4, Recommanded Product: Dbco-maleimide.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia