Matches in SemOpenAlex for { <https://semopenalex.org/work/W2890847308> ?p ?o ?g. }
- W2890847308 abstract "Thyroid-disrupting chemicals (TDCs) are xenobiotics that can interfere with the endocrine system and cause adverse effects in organisms and their offspring. TDCs affect both the thyroid gland and regulatory enzymes associated with thyroid hormone homeostasis. Transthyretin (TTR) is found in the serum and cerebrospinal fluid of vertebrates, where it transports thyroid hormones. Here, we explored the interspecies variation in TDC binding to human and fish TTR (exemplified by Gilthead seabream ( Sparus aurata)). The in vitro binding experiments showed that TDCs bind with equal or weaker affinity to seabream TTR than to the human TTR, in particular, the polar TDCs (>500-fold lower affinity). Crystal structures of the seabream TTR-TDC complexes revealed that all TDCs bound at the thyroid binding sites. However, amino acid substitution of Ser117 in human TTR to Thr117 in seabream prevented polar TDCs from binding deep in the hormone binding cavity, which explains their low affinity to seabream TTR. Molecular dynamics and in silico alanine scanning simulation also suggested that the protein backbone of seabream TTR is more rigid than the human one and that Thr117 provides fewer electrostatic contributions than Ser117 to ligand binding. This provides an explanation for the weaker affinities of the ligands that rely on electrostatic interactions with Thr117. The lower affinities of TDCs to fish TTR, in particular the polar ones, could potentially lead to milder thyroid-related effects in fish." @default.
- W2890847308 created "2018-09-27" @default.
- W2890847308 creator A5019666082 @default.
- W2890847308 creator A5022817762 @default.
- W2890847308 creator A5047896405 @default.
- W2890847308 creator A5053144750 @default.
- W2890847308 creator A5055204442 @default.
- W2890847308 creator A5058031847 @default.
- W2890847308 creator A5086307974 @default.
- W2890847308 creator A5088948647 @default.
- W2890847308 date "2018-10-02" @default.
- W2890847308 modified "2023-10-14" @default.
- W2890847308 title "Interspecies Variation between Fish and Human Transthyretins in Their Binding of Thyroid-Disrupting Chemicals" @default.
- W2890847308 cites W1573875184 @default.
- W2890847308 cites W1774442395 @default.
- W2890847308 cites W1892158199 @default.
- W2890847308 cites W189796632 @default.
- W2890847308 cites W1947279050 @default.
- W2890847308 cites W1971054145 @default.
- W2890847308 cites W1977021635 @default.
- W2890847308 cites W1985605677 @default.
- W2890847308 cites W1985744934 @default.
- W2890847308 cites W1986461448 @default.
- W2890847308 cites W1993885405 @default.
- W2890847308 cites W1994621940 @default.
- W2890847308 cites W1995676967 @default.
- W2890847308 cites W1996423252 @default.
- W2890847308 cites W2015165539 @default.
- W2890847308 cites W2020069279 @default.
- W2890847308 cites W2023158177 @default.
- W2890847308 cites W2023819857 @default.
- W2890847308 cites W2025125596 @default.
- W2890847308 cites W2025817299 @default.
- W2890847308 cites W2026765020 @default.
- W2890847308 cites W2029778081 @default.
- W2890847308 cites W2046402638 @default.
- W2890847308 cites W2047478614 @default.
- W2890847308 cites W2049309442 @default.
- W2890847308 cites W2052360197 @default.
- W2890847308 cites W2053309581 @default.
- W2890847308 cites W2057199097 @default.
- W2890847308 cites W2057504258 @default.
- W2890847308 cites W2059392150 @default.
- W2890847308 cites W2065242456 @default.
- W2890847308 cites W2069160027 @default.
- W2890847308 cites W2074081460 @default.
- W2890847308 cites W2078836932 @default.
- W2890847308 cites W2081929055 @default.
- W2890847308 cites W2082054968 @default.
- W2890847308 cites W2089164938 @default.
- W2890847308 cites W2095167055 @default.
- W2890847308 cites W2097327668 @default.
- W2890847308 cites W2100492886 @default.
- W2890847308 cites W2108921801 @default.
- W2890847308 cites W2109115386 @default.
- W2890847308 cites W2109893209 @default.
- W2890847308 cites W2110541778 @default.
- W2890847308 cites W2110651591 @default.
- W2890847308 cites W2112852427 @default.
- W2890847308 cites W2122714144 @default.
- W2890847308 cites W2132024398 @default.
- W2890847308 cites W2136959060 @default.
- W2890847308 cites W2139249147 @default.
- W2890847308 cites W2142868265 @default.
- W2890847308 cites W2144081223 @default.
- W2890847308 cites W2150181779 @default.
- W2890847308 cites W2152780287 @default.
- W2890847308 cites W2154119752 @default.
- W2890847308 cites W2158139019 @default.
- W2890847308 cites W2159447302 @default.
- W2890847308 cites W2162358004 @default.
- W2890847308 cites W2163341755 @default.
- W2890847308 cites W2166000089 @default.
- W2890847308 cites W2167803942 @default.
- W2890847308 cites W2180229411 @default.
- W2890847308 cites W2197302318 @default.
- W2890847308 cites W2326398335 @default.
- W2890847308 cites W2329183655 @default.
- W2890847308 cites W2342106571 @default.
- W2890847308 cites W2399042226 @default.
- W2890847308 cites W2526635653 @default.
- W2890847308 cites W2531327295 @default.
- W2890847308 cites W2561470806 @default.
- W2890847308 cites W4232829266 @default.
- W2890847308 cites W4235939487 @default.
- W2890847308 cites W4248872320 @default.
- W2890847308 doi "https://doi.org/10.1021/acs.est.8b03581" @default.
- W2890847308 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30226982" @default.
- W2890847308 hasPublicationYear "2018" @default.
- W2890847308 type Work @default.
- W2890847308 sameAs 2890847308 @default.
- W2890847308 citedByCount "4" @default.
- W2890847308 countsByYear W28908473082022 @default.
- W2890847308 countsByYear W28908473082023 @default.
- W2890847308 crossrefType "journal-article" @default.
- W2890847308 hasAuthorship W2890847308A5019666082 @default.
- W2890847308 hasAuthorship W2890847308A5022817762 @default.
- W2890847308 hasAuthorship W2890847308A5047896405 @default.
- W2890847308 hasAuthorship W2890847308A5053144750 @default.
- W2890847308 hasAuthorship W2890847308A5055204442 @default.