4fi7

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4fi7]] 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=4FI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FI7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4fi7]] 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=4FI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FI7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0UA:3-[5-(3,5-DICHLORO-4-HYDROXYPHENYL)-1,3,4-OXADIAZOL-2-YL]BENZENESULFONYL+FLUORIDE'>0UA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.402&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0UA:3-[5-(3,5-DICHLORO-4-HYDROXYPHENYL)-1,3,4-OXADIAZOL-2-YL]BENZENESULFONYL+FLUORIDE'>0UA</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=4fi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fi7 OCA], [https://pdbe.org/4fi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fi7 RCSB], [https://www.ebi.ac.uk/pdbsum/4fi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fi7 ProSAT]</span></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=4fi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fi7 OCA], [https://pdbe.org/4fi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fi7 RCSB], [https://www.ebi.ac.uk/pdbsum/4fi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fi7 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== 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>
[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>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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Molecules that bind selectively to a given protein and then undergo a rapid chemoselective reaction to form a covalent conjugate have utility in drug development. Herein a library of 1,3,4-oxadiazoles substituted at the 2 position with an aryl sulfonyl fluoride and at the 5 position with a substituted aryl known to have high affinity for the inner thyroxine binding subsite of transthyretin (TTR) was conceived of by structure-based design principles and was chemically synthesized. When bound in the thyroxine binding site, most of the aryl sulfonyl fluorides react rapidly and chemoselectively with the pK(a)-perturbed K15 residue, kinetically stabilizing TTR and thus preventing amyloid fibril formation, known to cause polyneuropathy. Conjugation t(50)s range from 1 to 4 min, approximately 1400 times faster than the hydrolysis reaction outside the thyroxine binding site. X-ray crystallography confirms the anticipated binding orientation and sheds light on the sulfonyl fluoride activation leading to the sulfonamide linkage to TTR. Eleven of the aryl sulfonyl fluorides efficiently form conjugates with TTR in plasma. Eleven of the TTR covalent kinetic stabilizers synthesized exhibit fluorescence upon conjugation and therefore could have imaging applications as a consequence of the environment sensitive fluorescence of the chromophore.
 
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Aromatic Sulfonyl Fluorides Covalently Kinetically Stabilize Transthyretin to Prevent Amyloidogenesis while Affording a Fluorescent Conjugate.,Grimster NP, Connelly S, Baranczak A, Dong J, Krasnova LB, Sharpless KB, Powers ET, Wilson IA, Kelly JW J Am Chem Soc. 2013 Feb 14. PMID:23350654<ref>PMID:23350654</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 4fi7" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==

Revision as of 15:25, 14 March 2024

Kinetic Stabilization of transthyretin through covalent modification of K15 by 3-(5-(3,5-dichloro-4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)-benzenesulfonamide

PDB ID 4fi7

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