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• W1976819985 abstract "d-Cycloserine is a second-line drug approved for use in the treatment of patients infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. The unique mechanism of action of d-cycloserine, compared with those of other clinically employed antimycobacterial agents, represents an untapped and exploitable resource for future rational drug design programs. Here, we show that d-cycloserine is a slow-onset inhibitor of MtDdl and that this behavior is specific to the M. tuberculosis enzyme orthologue. Furthermore, evidence is presented that indicates d-cycloserine binds exclusively to the C-terminal d-alanine binding site, even in the absence of bound d-alanine at the N-terminal binding site. Together, these results led us to propose a new model of d-alanine:d-alanine ligase inhibition by d-cycloserine and suggest new opportunities for rational drug design against an essential, clinically validated mycobacterial target." @default.
• W1976819985 created "2016-06-24" @default.
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• W1976819985 date "2013-09-25" @default.
• W1976819985 modified "2023-10-04" @default.
• W1976819985 title "Reinterpreting the Mechanism of Inhibition of <i>Mycobacterium tuberculosis</i> <scp>d</scp>-Alanine:<scp>d</scp>-Alanine Ligase by <scp>d</scp>-Cycloserine" @default.
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• W1976819985 doi "https://doi.org/10.1021/bi400839f" @default.
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