6knv | pdb_00006knv

THRb mutation with a novel agonist

spinqualitylabelsall models 6knv, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6knv is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 8HO Related: 6kkb Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [THB_HUMAN] Defects in THRB are the cause of generalized thyroid hormone resistance (GTHR) [MIM:188570]. GTHR is a disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Defects in THRB are the cause of generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:274300]. An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. Defects in THRB are the cause of selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]; also known as familial hyperthyroidism due to inappropriate thyrotropin secretion. PRTH is a variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. [NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. Function [THB_HUMAN] High affinity receptor for triiodothyronine. [NCOA2_HUMAN] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Publication Abstract from PubMed Nuclear receptors are important transcriptional factors that share high sequence identity and conserved domains, including a DNA-binding domain (DBD) and a ligand-binding domain (LBD). The LBD plays a crucial role in ligand-mediated nuclear receptor activity. Hundreds of different crystal structures of nuclear receptors have revealed a general mechanism for the molecular basis of ligand binding and ligand-mediated regulation of nuclear receptors. Despite the conserved fold of nuclear receptor LBDs, the ligand-binding pocket is the least conserved region among different nuclear receptor LBDs. Structural comparison and analysis show that several features of the pocket, like the size and also the shape, have contributed to the ligand binding affinity and specificity. In addition, the plastic nature of the ligand-binding pockets in many nuclear receptors provides greater flexibility to further accommodate specific ligands with a variety of conformations. Nuclear receptor coactivators usually contain multiple LXXLL motifs that are used to interact with nuclear receptors. The nuclear receptors respond differently to distinct ligands and readily exchange their ligands in different environments. The conformational flexibility of the AF-2 helix allows the nuclear receptor to sense the presence of the bound ligands, either an agonist or an antagonist, and to recruit the coactivators or corepressors that ultimately determine the transcriptional activation or repression of nuclear receptors. Structural and functional insights into nuclear receptor signaling.,Jin L, Li Y Adv Drug Deliv Rev. 2010 Oct 30;62(13):1218-26. doi: 10.1016/j.addr.2010.08.007. , Epub 2010 Aug 17. PMID:20723571 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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