View source for 9jiu


==Ferritin mutant R63MeHis==
<StructureSection load='9jiu' size='340' side='right'caption='[[9jiu]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9jiu]] is a 12 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=9JIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JIU 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]] 2.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MHS:N1-METHYLATED+HISTIDINE'>MHS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</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=9jiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jiu OCA], [https://pdbe.org/9jiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jiu RCSB], [https://www.ebi.ac.uk/pdbsum/9jiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jiu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FRIH_HUMAN FRIH_HUMAN] Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).
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== Publication Abstract from PubMed ==
Histidine modifications of proteins are broadly based on chemical methods triggering N-substitution reactions such as aza-Michael addition at histidine's moderately nucleophilic imidazole side chain. While recent studies have demonstrated chemoselective, histidine-specific modifications by further exploiting imidazole's electrophilic reactivity to overcome interference from the more nucleophilic lysine and cysteine, achieving site-specific histidine modifications remains a major challenge due to the absence of spatial control over chemical processes. Herein, through X-ray crystallography and cryo-electron microscopy structural studies, we describe the rational design of a nature-inspired, noncanonical amino-acid-incorporated, human ferritin-based metalloenzyme that is capable of introducing site-specific post-translational modifications (PTMs) to histidine in peptides and proteins. Specifically, chemoenzymatic aza-Michael additions on single histidine residues were carried out on eight protein substrates ranging from 10 to 607 amino acids including the insulin peptide hormone. By introducing an insulin-targeting peptide into our metalloenzyme, we further directed modifications to be carried out site-specifically on insulin's B-chain histidine 5. The success of this biocatalysis platform outlines a novel approach in introducing residue- and, moreover, site-specific post-translational modifications to peptides and proteins, which may further enable reactions to be carried out in vivo.

Site-Specific Histidine Aza-Michael Addition in Proteins Enabled by a Ferritin-Based Metalloenzyme.,Tsou JC, Tsou CJ, Wang CH, Ko AA, Wang YH, Liang HH, Sun JC, Huang KF, Ko TP, Lin SY, Wang YS J Am Chem Soc. 2024 Nov 5. doi: 10.1021/jacs.4c14446. PMID:39499210<ref>PMID:39499210</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9jiu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Huang K-F]]
[[Category: Ko T-P]]
[[Category: Tsou J-C]]
[[Category: Wang Y-S]]