4pmf

Human transthyretin (TTR) complexed with curcumin

spinqualitylabelsall models 4pmf, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pmf is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CUR, EDO, NA Related: 4pme, 4pm1 Resources: FirstGlance, OCA, RCSB, PDBsum Disease [TTHY_HUMAN] Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:105210]. A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor. Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:145680]. It is a condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:115430]. It is a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis. Function [TTHY_HUMAN] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain. Publication Abstract from PubMed Crystallographic structure determination of protein-ligand complexes of transthyretin (TTR) has been hindered by the low affinity of many compounds that bind to the central cavity of the tetramer. Because crystallization trials are carried out at protein and ligand concentration that approach the millimolar range, low affinity is less of a problem than the poor solubility of many compounds that have been shown to inhibit amyloid fibril formation. To achieve complete occupancy in co-crystallization experiments, the minimal requirement is one ligand for each of the two sites within the TTR tetramer. Here we present a new strategy for the co-crystallization of TTR using high molecular weight polyethylene glycol instead of high ionic strength precipitants, with ligands solubilized in multicomponent mixtures of compounds. This strategy is applied to the crystallization of TTR complexes with curcumin and 16alpha-bromo-estradiol and report the crystal structures with these compounds and with the ferulic acid the result of curcumin degradation. Transthyretin complexes with curcumin and bromo-estradiol: evaluation of solubilizing multicomponent mixtures.,Ciccone L, Tepshi L, Nencetti S, Stura EA N Biotechnol. 2014 Sep 16. pii: S1871-6784(14)02165-7. doi:, 10.1016/j.nbt.2014.09.002. PMID:25224922 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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