Liothyronine(T3)

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(New page: '''Liothyronine(T3)''' Pubchem(5920) A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from p...)
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Comment Thyroid hormone
Comment Thyroid hormone
More active than T4
More active than T4
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{| border="1;width:100%; height:200px;style=text-align:center"
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MMDB ID: 10776
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|+'''Table I:'''
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PDB ID: 1BSX
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Reference: Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KRStructure and specificity of nuclear receptor-coactivator interactionsGenes Dev. v12, p.3343-3356
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! style="background:brown; color:white" |MMDB ID
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Combinatorial regulation of transcription implies flexible yet precise assembly of multiprotein regulatory complexes in response to signals. Biochemical and crystallographic analyses revealed that hormone binding leads to the formation of a hydrophobic groove within the ligand binding domain (LBD) of the thyroid hormone receptor that interacts with an LxxLL motif-containing alpha-helix from GRIP1, a coactivator....
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! style="background:brown; color:white" |PDB ID  
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! style="background:brown; color:white" |Reference
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MMDB ID: 28583
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|-
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PDB ID: 1SN5
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|10776
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Reference: Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AEHigh resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxineJ. Biol. Chem. v279, p.26411-26416
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|1BSX
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Transthyretin (TTR) is an extracellular transport protein involved in the distribution of thyroid hormones and vitamin A. So far, TTR has only been found in vertebrates, of which piscine TTR displays the lowest sequence identity with human TTR (47%). Human and piscine TTR bind both thyroid hormones 3,5,3"-triiodo-l-thyronine (T(3)) and 3,5,3",5"-tetraiodo-l-thyronine (thyroxine, T(4))..
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|Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KRStructure and specificity of nuclear receptor-coactivator interactionsGenes Dev. v12, p.3343-3356
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+
|-
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MMDB ID: 31718
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|28583
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PDB ID: 1XZX
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|1SN5
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Reference: Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Cunha Lima ST, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JDThyroxine-thyroid hormone receptor interactionsJ. Biol. Chem. v279, p.55801-55808
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|Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AEHigh resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxineJ. Biol. Chem. v279, p.26411-26416
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Thyroid hormone (TH) actions are mediated by nuclear receptors (TRs alpha and beta) that bind triiodothyronine (T(3), 3,5,3"-triiodo-l-thyronine) with high affinity, and its precursor thyroxine (T(4), 3,5,3",5"-tetraiodo-l-thyronine) with lower affinity. T(4) contains a bulky 5" iodine group absent from T(3). Because T(3) is buried in the core of the ligand binding domain (LBD), we have predicted that TH analogues with 5" substituents should fit poorly into the ligand binding pocket and perhaps behave as antagonists....
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|-
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|31718
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MMDB ID: 40533
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|1XZX
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PDB ID: 2H6W
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|Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Cunha Lima ST, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JDThyroxine-thyroid hormone receptor interactionsJ. Biol. Chem. v279, p.55801-55808
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|-
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MMDB ID: 40534
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|40533
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PDB ID: 2H77
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|2H6W
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|Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
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MMDB ID: 40535
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|-
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|40534
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|2H77
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|Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
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|40535
PDB ID: 2H79
PDB ID: 2H79
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|Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
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Reference: Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
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The thyroid hormone receptor (TR) D-domain links the ligand-binding domain (LBD, EF-domain) to the DNA-binding domain (DBD, C-domain), but its structure, and even its existence as a functional unit, are controversial. The D domain is poorly conserved throughout the nuclear receptor family and was originally proposed to comprise an unfolded hinge that facilitates rotation between the LBD and the DBD....
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|59297
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|2PIV
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MMDB ID: 59297
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|Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079
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PDB ID: 2PIV
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|-
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|59298
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MMDB ID: 59298
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|2PIW
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PDB ID: 2PIW
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|Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079
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+
|-
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Reference: Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079
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Current approaches to inhibit nuclear receptor (NR) activity target the hormone binding pocket but face limitations. We have proposed that inhibitors, which bind to nuclear receptor surfaces that mediate assembly of the receptor"s binding partners, might overcome some of these limitations. The androgen receptor (AR) plays a central role in prostate cancer, but conventional inhibitors lose effectiveness as cancer treatments because anti-androgen resistance usually develops....
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Physical Property  Value  Units  Temp (deg C)  Source
Physical Property  Value  Units  Temp (deg C)  Source

Revision as of 06:11, 24 October 2008

Liothyronine(T3)

Pubchem(5920)

A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.

KEGG Pathway(C02465) Tyrosine metabolism Neuroactive ligand-receptor interaction Autoimmune thyroid disease Comment Thyroid hormone More active than T4

Physical Property Value Units Temp (deg C) Source Melting Point 236.5 dec deg C EXP log P (octanol-water) 2.960 (none) EST Water Solubility 3.96 mg/L 37 EXP Vapor Pressure 3.90E-16 mm Hg 25 EST Henry's Law Constant 3.41E-18 atm-m3/mole 25 EST Atmospheric OH Rate Constant 4.82E-11 cm3/molecule-sec 25 EST Organism Test Type Route Reported Dose (Normalized Dose) Effect Source rat LDLo oral 7500mg/kg (7500mg/kg) Roczniki Panstwowego Zakladu Higieny. Vol. 32, Pg. 197, 1981. Reference1 Nature Chemical Biology 4, 548 - 556 (2008) Published online: 10 August 2008 | doi:10.1038/nchembio.106 Cytosporone B is an agonist for nuclear orphan receptor Nur77 Yanyan Zhan1,3, Xiping Du1,3, Hangzi Chen1, Jingjing Liu1, Bixing Zhao1, Danhong Huang1, Guideng Li1, Qingyan Xu1, Mingqing Zhang1, Bart C Weimer2, Dong Chen2, Zhe Cheng1, Lianru Zhang1, Qinxi Li1, Shaowei Li1, Zhonghui Zheng1, Siyang Song1, Yaojian Huang1, Zhiyun Ye1, Wenjin Su1, Sheng-Cai Lin1, Yuemao Shen1 & Qiao Wu1 Abstract Nuclear orphan receptor Nur77 has important roles in many biological processes. However, a physiological ligand for Nur77 has not been identified. Here, we report that the octaketide cytosporone B (Csn-B) is a naturally occurring agonist for Nur77. Csn-B specifically binds to the ligand-binding domain of Nur77 and stimulates Nur77-dependent transactivational activity towards target genes including Nr4a1 (Nur77) itself, which contains multiple consensus response elements allowing positive autoregulation in a Csn-B–dependent manner. Csn-B also elevates blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis. These biological effects were not observed in Nur77-null (Nr4a1-/-) mice, which indicates that Csn-B regulates gluconeogenesis through Nur77. Moreover, Csn-B induced apoptosis and retarded xenograft tumor growth by inducing Nur77 expression, translocating Nur77 to mitochondria to cause cytochrome c release. Thus, Csn-B may represent a promising therapeutic drug for cancers and hypoglycemia, and it may also be useful as a reagent to increase understanding of Nur77 biological function.
Table I:
MMDB ID PDB ID Reference
10776 1BSX Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KRStructure and specificity of nuclear receptor-coactivator interactionsGenes Dev. v12, p.3343-3356
28583 1SN5 Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AEHigh resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxineJ. Biol. Chem. v279, p.26411-26416
31718 1XZX Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Cunha Lima ST, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JDThyroxine-thyroid hormone receptor interactionsJ. Biol. Chem. v279, p.55801-55808
40533 2H6W Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
40534 2H77 Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
40535

PDB ID: 2H79

Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Ne, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov IStructural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor functionJ. Mol. Biol. v360, p.586-598
59297 2PIV Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079
59298 2PIW Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJA surface on the androgen receptor that allosterically regulates coactivator bindingProc. Natl. Acad. Sci. U. S. A. v104, p.16074-16079
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