8aww

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 8aww is ON HOLD until Paper Publication
+
==Transthyretin conjugated with a tafamidis derivative==
 +
<StructureSection load='8aww' size='340' side='right'caption='[[8aww]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[8aww]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AWW FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OIT:~{N}-(6-azanylhexyl)-2-[3,5-bis(chloranyl)phenyl]-1,3-benzoxazole-6-carboxamide'>OIT</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8aww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aww OCA], [https://pdbe.org/8aww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aww RCSB], [https://www.ebi.ac.uk/pdbsum/8aww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aww ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN] Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:[https://omim.org/entry/105210 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.<ref>PMID:11243784</ref> <ref>PMID:15735344</ref> <ref>PMID:19167329</ref> <ref>PMID:3818577</ref> <ref>PMID:3022108</ref> <ref>PMID:6651852</ref> <ref>PMID:6583672</ref> <ref>PMID:3135807</ref> <ref>PMID:1517749</ref> <ref>PMID:1932142</ref> <ref>PMID:7923855</ref> <ref>PMID:8382610</ref> <ref>PMID:8428915</ref> <ref>PMID:9733771</ref> <ref>PMID:12403615</ref> <ref>PMID:16185074</ref> <ref>PMID:16627944</ref> <ref>PMID:6487335</ref> <ref>PMID:3722385</ref> <ref>PMID:2891727</ref> <ref>PMID:2161654</ref> <ref>PMID:2363717</ref> <ref>PMID:1656975</ref> <ref>PMID:2046936</ref> <ref>PMID:1570831</ref> <ref>PMID:1734866</ref> <ref>PMID:1520326</ref> <ref>PMID:1520336</ref> <ref>PMID:1544214</ref> <ref>PMID:1351039</ref> <ref>PMID:1301926</ref> <ref>PMID:1362222</ref> <ref>PMID:1436517</ref> <ref>PMID:8352764</ref> <ref>PMID:8038017</ref> <ref>PMID:8257997</ref> <ref>PMID:8095302</ref> <ref>PMID:1997217</ref> <ref>PMID:8019560</ref> <ref>PMID:8081397</ref> <ref>PMID:7914929</ref> <ref>PMID:8133316</ref> <ref>PMID:7910950</ref> <ref>PMID:7655883</ref> <ref>PMID:7850982</ref> <ref>PMID:8579098</ref> <ref>PMID:9066351</ref> <ref>PMID:8990019</ref> <ref>PMID:9605286</ref> <ref>PMID:10036587</ref> <ref>PMID:10627135</ref> <ref>PMID:10694917</ref> <ref>PMID:10211412</ref> <ref>PMID:10439117</ref> <ref>PMID:10611950</ref> <ref>PMID:10071047</ref> <ref>PMID:10436378</ref> <ref>PMID:10842705</ref> <ref>PMID:10842718</ref> <ref>PMID:10882995</ref> <ref>PMID:11445644</ref> <ref>PMID:12557757</ref> <ref>PMID:11866053</ref> <ref>PMID:12050338</ref> <ref>PMID:12771253</ref> <ref>PMID:15214015</ref> <ref>PMID:15478468</ref> <ref>PMID:15217993</ref> <ref>PMID:17453626</ref> <ref>PMID:17577687</ref> <ref>PMID:17503405</ref> <ref>PMID:17635579</ref> Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:[https://omim.org/entry/145680 145680]. It is a condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.<ref>PMID:1979335</ref> Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:[https://omim.org/entry/115430 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.<ref>PMID:8309582</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Several protein-drug conjugates are currently being used in cancer therapy. These conjugates rely on cytotoxic organic compounds that are covalently attached to the carrier proteins or that interact with them via non-covalent interactions. Human transthyretin (TTR), a physiological protein, has already been identified as a possible carrier protein for the delivery of cytotoxic drugs. Here we show the structure-guided development of a new stable cytotoxic molecule based on a known strong binder of TTR and a well-established anticancer drug. This example is used to demonstrate the importance of the integration of multiple biophysical and structural techniques, encompassing microscale thermophoresis, X-ray crystallography and NMR. In particular, we show that solid-state NMR has the ability to reveal effects caused by ligand binding which are more easily relatable to structural and dynamical alterations that impact the stability of macromolecular complexes.
-
Authors: Cerofolini, L., Vasa, K., Bianconi, E., Salobehaj, M., Cappelli, G., Licciardi, G., Perez-Rafols, A., Padilla Cortes, L.D., Antonacci, S., Rizzo, D., Ravera, E., Calderone, V., Parigi, G., Luchinat, C., Macchiarulo, A., Menichetti, S., Fragai, M.
+
Combining Solid-State NMR with Structural and Biophysical Techniques to Design Challenging Protein-Drug Conjugates.,Cerofolini L, Vasa K, Bianconi E, Salobehaj M, Cappelli G, Bonciani A, Licciardi G, Perez-Rafols A, Padilla-Cortes L, Antonacci S, Rizzo D, Ravera E, Viglianisi C, Calderone V, Parigi G, Luchinat C, Macchiarulo A, Menichetti S, Fragai M Angew Chem Int Ed Engl. 2023 Jun 5:e202303202. doi: 10.1002/anie.202303202. PMID:37276329<ref>PMID:37276329</ref>
-
Description: Transthyretin conjugated with a tafamidis derivative
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Calderone, V]]
+
<div class="pdbe-citations 8aww" style="background-color:#fffaf0;"></div>
-
[[Category: Parigi, G]]
+
== References ==
-
[[Category: Licciardi, G]]
+
<references/>
-
[[Category: Fragai, M]]
+
__TOC__
-
[[Category: Cappelli, G]]
+
</StructureSection>
-
[[Category: Padilla Cortes, L.D]]
+
[[Category: Homo sapiens]]
-
[[Category: Menichetti, S]]
+
[[Category: Large Structures]]
-
[[Category: Antonacci, S]]
+
[[Category: Antonacci S]]
-
[[Category: Macchiarulo, A]]
+
[[Category: Bianconi E]]
-
[[Category: Bianconi, E]]
+
[[Category: Calderone V]]
-
[[Category: Luchinat, C]]
+
[[Category: Cappelli G]]
-
[[Category: Vasa, K]]
+
[[Category: Cerofolini L]]
-
[[Category: Perez-Rafols, A]]
+
[[Category: Fragai M]]
-
[[Category: Cerofolini, L]]
+
[[Category: Licciardi G]]
-
[[Category: Rizzo, D]]
+
[[Category: Luchinat C]]
-
[[Category: Ravera, E]]
+
[[Category: Macchiarulo A]]
-
[[Category: Salobehaj, M]]
+
[[Category: Menichetti S]]
 +
[[Category: Padilla Cortes LD]]
 +
[[Category: Parigi G]]
 +
[[Category: Perez-Rafols A]]
 +
[[Category: Ravera E]]
 +
[[Category: Rizzo D]]
 +
[[Category: Salobehaj M]]
 +
[[Category: Vasa K]]

Revision as of 07:14, 12 July 2023

Transthyretin conjugated with a tafamidis derivative

PDB ID 8aww

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8aww"
Personal tools