Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386878412> ?p ?o ?g. }
- W4386878412 endingPage "13" @default.
- W4386878412 startingPage "1" @default.
- W4386878412 abstract "Clinical resistance against bedaquiline (BDQ) remains intractable to anti-tuberculosis therapies since its introduction to the market over a decade ago. Herein, we investigated the structural and mechanical aspects of BDQ resistance in AtpE, MmpR5, and PepQ. The known target-specific resistant single non-synonymous mutations were refined to high-grade candidates. Thus, 7 (AtpE), 5 (MmpR5), and 1 (PepQ) single nucleotide polymorphisms (SNPs) and one insertion frameshift mutation in MmpR5 were recreated at the molecular level, and these phenotypic models were then directed to stringent dynamics to define time-scaled changes. The AtpE variants destabilized the structure; mainly, L59V, E61D, and I66M were detrimental to the complex fitness, while L74V and L114P boosted the BDQ binding to MmpR5. The first three and last two alterations gave rise to loss- and gain-of-function to AtpE and MmpR5, respectively. Hence, these five mutants are functionally relevant and therapeutically targetable hotspots of BDQ resistance. There were no noticeable changes in PepQ data analysis. The present study revealed that MmpR5 mutations confer BDQ resistance, whereas AtpE and PepQ SNPs display low susceptibility. These results were tallied with the published findings, which testified to the pursued method's reliability and accuracy. We hope these data and inferences could be helpful for the futuristic design of novel TB drugs.Communicated by Ramaswamy H. Sarma." @default.
- W4386878412 created "2023-09-21" @default.
- W4386878412 creator A5011457283 @default.
- W4386878412 creator A5047495964 @default.
- W4386878412 creator A5064051366 @default.
- W4386878412 creator A5065236650 @default.
- W4386878412 creator A5084230820 @default.
- W4386878412 creator A5084569212 @default.
- W4386878412 creator A5086650018 @default.
- W4386878412 date "2023-09-20" @default.
- W4386878412 modified "2023-09-27" @default.
- W4386878412 title "<i>In silico</i> structural and mechanical insights into bedaquiline resistance associated with high-grade non-synonymous mutations in <i>atpE</i> , <i>mmpR5</i> , and <i>pepQ</i>" @default.
- W4386878412 cites W1972758026 @default.
- W4386878412 cites W1990771438 @default.
- W4386878412 cites W1991874243 @default.
- W4386878412 cites W2004370520 @default.
- W4386878412 cites W2005166795 @default.
- W4386878412 cites W2009326252 @default.
- W4386878412 cites W2011301426 @default.
- W4386878412 cites W2021520922 @default.
- W4386878412 cites W2028046413 @default.
- W4386878412 cites W2029667189 @default.
- W4386878412 cites W2038532826 @default.
- W4386878412 cites W2038758364 @default.
- W4386878412 cites W2055092907 @default.
- W4386878412 cites W2056981303 @default.
- W4386878412 cites W2057664120 @default.
- W4386878412 cites W2060872117 @default.
- W4386878412 cites W2063563543 @default.
- W4386878412 cites W2066414494 @default.
- W4386878412 cites W2067174909 @default.
- W4386878412 cites W2069197202 @default.
- W4386878412 cites W2070753604 @default.
- W4386878412 cites W2090640084 @default.
- W4386878412 cites W2095719702 @default.
- W4386878412 cites W2103945336 @default.
- W4386878412 cites W2105668062 @default.
- W4386878412 cites W2106140689 @default.
- W4386878412 cites W2109154308 @default.
- W4386878412 cites W2118200955 @default.
- W4386878412 cites W2120619607 @default.
- W4386878412 cites W2122732537 @default.
- W4386878412 cites W2122797777 @default.
- W4386878412 cites W2134762386 @default.
- W4386878412 cites W2134967712 @default.
- W4386878412 cites W2136007937 @default.
- W4386878412 cites W2146344189 @default.
- W4386878412 cites W2147533449 @default.
- W4386878412 cites W2150469424 @default.
- W4386878412 cites W2158658436 @default.
- W4386878412 cites W2159526017 @default.
- W4386878412 cites W2167315117 @default.
- W4386878412 cites W2168269595 @default.
- W4386878412 cites W2171190919 @default.
- W4386878412 cites W2175636570 @default.
- W4386878412 cites W2206954826 @default.
- W4386878412 cites W2266076319 @default.
- W4386878412 cites W2337812067 @default.
- W4386878412 cites W2343134315 @default.
- W4386878412 cites W2397080465 @default.
- W4386878412 cites W2405075761 @default.
- W4386878412 cites W2563852803 @default.
- W4386878412 cites W2568617656 @default.
- W4386878412 cites W2612598385 @default.
- W4386878412 cites W2765670399 @default.
- W4386878412 cites W2804139804 @default.
- W4386878412 cites W2905232362 @default.
- W4386878412 cites W2907111821 @default.
- W4386878412 cites W2909070815 @default.
- W4386878412 cites W2946332609 @default.
- W4386878412 cites W2947097964 @default.
- W4386878412 cites W2978287172 @default.
- W4386878412 cites W3000056609 @default.
- W4386878412 cites W3022473231 @default.
- W4386878412 cites W3046751266 @default.
- W4386878412 cites W3082225610 @default.
- W4386878412 cites W3088102352 @default.
- W4386878412 cites W3130549637 @default.
- W4386878412 cites W3168436232 @default.
- W4386878412 cites W3196454029 @default.
- W4386878412 cites W3202639926 @default.
- W4386878412 cites W3205376684 @default.
- W4386878412 cites W3212793290 @default.
- W4386878412 cites W3213922610 @default.
- W4386878412 cites W4318979003 @default.
- W4386878412 doi "https://doi.org/10.1080/07391102.2023.2259486" @default.
- W4386878412 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37728541" @default.
- W4386878412 hasPublicationYear "2023" @default.
- W4386878412 type Work @default.
- W4386878412 citedByCount "0" @default.
- W4386878412 crossrefType "journal-article" @default.
- W4386878412 hasAuthorship W4386878412A5011457283 @default.
- W4386878412 hasAuthorship W4386878412A5047495964 @default.
- W4386878412 hasAuthorship W4386878412A5064051366 @default.
- W4386878412 hasAuthorship W4386878412A5065236650 @default.
- W4386878412 hasAuthorship W4386878412A5084230820 @default.
- W4386878412 hasAuthorship W4386878412A5084569212 @default.
- W4386878412 hasAuthorship W4386878412A5086650018 @default.