Disulfide Isomerization in nDsbD-DsbC Complex - Exploring an Internal Nucleophile Mediated Reaction Pathway.
Aparna G NairD Sravanakumar PerumallaPadmesh AnjukandiPublished in: Chemphyschem : a European journal of chemical physics and physical chemistry (2022)
The disulfide bond redox chemistry of proteins is believed to be mostly governed by the proton motive force. The nucleophilic and α-elimination mechanisms are also found to supplement the formation and scission of the S-S bonds. On these grounds, the possibility for an internal nucleophile assisted disulfide bond formation in the nDsbD-DsbC complex was proposed way back. Using QM/MM MD metadynamics simulations, we explore the feasibility of the proposed mechanism. Our simulations highlight the formation of the internal nucleophile Tyr 42 O - and Tyr 40 O - which further generates Cys 103 S - necessary for the disulfide bond formation in nDsbD. Our results illustrate how the isomerase DsbC is functionally activated by nDsbD in gram-negative bacteria. Also, we foresee that the results will be important for modelling anti-bacterial compounds based on nDsbD.
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