Matches in SemOpenAlex for { <https://semopenalex.org/work/W4291377974> ?p ?o ?g. }
- W4291377974 abstract "Human tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in the synthesis of serotonin. Its dysfunction has been implicated in various psychiatric disorders such as depression, autism, and bipolar disorder. TPH2 is typically decreased in stability and catalytic activity in patients; thus, screening of molecules capable of binding and stabilizing the structure of TPH2 in activated conformation is desired for drug development in mental disorder treatment. Here, we solved the 3.0 Å cryo-EM structure of the TPH2 tetramer. Then, based on the structure, we conducted allosteric site prediction and small-molecule activator screening to the obtained cavity. ZINC000068568685 was successfully selected as the best candidate with highest binding affinity. To better understand the driving forces and binding stability of the complex, we performed molecular dynamics simulation, which indicates that ZINC000068568685 has great potential to stabilize the folding of the TPH2 tetramer to facilitate its activity. The research might shed light on the development of novel drugs targeting TPH2 for the treatment of psychological disorders." @default.
- W4291377974 created "2022-08-15" @default.
- W4291377974 creator A5002288609 @default.
- W4291377974 creator A5002597734 @default.
- W4291377974 creator A5025222082 @default.
- W4291377974 creator A5025787180 @default.
- W4291377974 creator A5028296024 @default.
- W4291377974 creator A5034505488 @default.
- W4291377974 date "2022-08-15" @default.
- W4291377974 modified "2023-10-15" @default.
- W4291377974 title "Cryo-EM Structure and Activator Screening of Human Tryptophan Hydroxylase 2" @default.
- W4291377974 cites W1512801428 @default.
- W4291377974 cites W1564508078 @default.
- W4291377974 cites W1886822464 @default.
- W4291377974 cites W1965726341 @default.
- W4291377974 cites W1967348240 @default.
- W4291377974 cites W1973799412 @default.
- W4291377974 cites W1974294420 @default.
- W4291377974 cites W1976114760 @default.
- W4291377974 cites W1978271321 @default.
- W4291377974 cites W1983308408 @default.
- W4291377974 cites W1983475717 @default.
- W4291377974 cites W1988107743 @default.
- W4291377974 cites W1990948097 @default.
- W4291377974 cites W1996234987 @default.
- W4291377974 cites W1997388457 @default.
- W4291377974 cites W1998265250 @default.
- W4291377974 cites W2024553195 @default.
- W4291377974 cites W2028054765 @default.
- W4291377974 cites W2029667189 @default.
- W4291377974 cites W2033032732 @default.
- W4291377974 cites W2035663126 @default.
- W4291377974 cites W2061855305 @default.
- W4291377974 cites W2074473216 @default.
- W4291377974 cites W2077726906 @default.
- W4291377974 cites W2094295346 @default.
- W4291377974 cites W2095487531 @default.
- W4291377974 cites W2102488356 @default.
- W4291377974 cites W2106848510 @default.
- W4291377974 cites W2108325842 @default.
- W4291377974 cites W2117296179 @default.
- W4291377974 cites W2117344541 @default.
- W4291377974 cites W2121621209 @default.
- W4291377974 cites W2129556489 @default.
- W4291377974 cites W2132629607 @default.
- W4291377974 cites W2135073823 @default.
- W4291377974 cites W2139629302 @default.
- W4291377974 cites W2144081223 @default.
- W4291377974 cites W2155948158 @default.
- W4291377974 cites W2158197814 @default.
- W4291377974 cites W2165164884 @default.
- W4291377974 cites W2168678503 @default.
- W4291377974 cites W2171571841 @default.
- W4291377974 cites W2180229411 @default.
- W4291377974 cites W2278468495 @default.
- W4291377974 cites W2329080044 @default.
- W4291377974 cites W2336507134 @default.
- W4291377974 cites W2339078872 @default.
- W4291377974 cites W2408522200 @default.
- W4291377974 cites W2418037503 @default.
- W4291377974 cites W2474609557 @default.
- W4291377974 cites W2475021010 @default.
- W4291377974 cites W2561058038 @default.
- W4291377974 cites W2561810782 @default.
- W4291377974 cites W2565042964 @default.
- W4291377974 cites W2593511418 @default.
- W4291377974 cites W2601063088 @default.
- W4291377974 cites W2759696454 @default.
- W4291377974 cites W2772977605 @default.
- W4291377974 cites W2793329686 @default.
- W4291377974 cites W2799327292 @default.
- W4291377974 cites W2896563748 @default.
- W4291377974 cites W2900405160 @default.
- W4291377974 cites W2901076936 @default.
- W4291377974 cites W2913315318 @default.
- W4291377974 cites W2930161903 @default.
- W4291377974 cites W2930394955 @default.
- W4291377974 cites W2942558631 @default.
- W4291377974 cites W2953320394 @default.
- W4291377974 cites W2980987186 @default.
- W4291377974 cites W2981507824 @default.
- W4291377974 cites W2982055388 @default.
- W4291377974 cites W2987526375 @default.
- W4291377974 cites W2999578678 @default.
- W4291377974 cites W3009445823 @default.
- W4291377974 cites W3010361345 @default.
- W4291377974 cites W3019541266 @default.
- W4291377974 cites W3048696230 @default.
- W4291377974 cites W3091822736 @default.
- W4291377974 cites W3123214675 @default.
- W4291377974 cites W3138052320 @default.
- W4291377974 cites W3157906237 @default.
- W4291377974 cites W3180153817 @default.
- W4291377974 cites W3210162216 @default.
- W4291377974 cites W3216267228 @default.
- W4291377974 doi "https://doi.org/10.3389/fphar.2022.907437" @default.
- W4291377974 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36046836" @default.
- W4291377974 hasPublicationYear "2022" @default.
- W4291377974 type Work @default.
- W4291377974 citedByCount "2" @default.