6ftv: Difference between revisions
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The | ==X-ray structure of human heavy chain ferritin in complex with NAMI A== | ||
<StructureSection load='6ftv' size='340' side='right' caption='[[6ftv]], [[Resolution|resolution]] 1.58Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ftv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FTV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FTV FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RU:RUTHENIUM+ION'>RU</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FTH1, FTH, FTHL6, OK/SW-cl.84, PIG15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ferroxidase Ferroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.16.3.1 1.16.3.1] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ftv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftv OCA], [http://pdbe.org/6ftv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ftv RCSB], [http://www.ebi.ac.uk/pdbsum/6ftv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The reaction of the antimetastatic ruthenium(iii) drug NAMI A with human H-chain ferritin (HuHf) was investigated through a variety of biophysical methods. We observed that the addition of HuHf to NAMI A solutions significantly increases the rate of spontaneous NAMI A hydrolysis suggesting the occurrence of a direct metallodrug-protein interaction. The resulting hydrolyzed Ru species binds the protein mostly forming a relatively tight 1 : 1 ruthenium/ferritin (subunit) adduct that was then separated and characterized. Notably, this adduct shows a characteristic CD spectrum in the visible region, which is diagnostic of the existence of at least one protein bound ruthenium center. The crystal structure of this NAMI A/HuHf adduct was subsequently solved at 1.58 A resolution; clear evidence is given for the selective binding of a single Ru ion to His105 of each subunit with concomitant release of all other original Ru ligands in agreement with previous observations. We also noted that NAMI A produces a partial inhibition of HuHf ferroxidase activity. The implications of the above results are discussed. | |||
The NAMI A - human ferritin system: a biophysical characterization.,Ciambellotti S, Pratesi A, Severi M, Ferraro G, Alessio E, Merlino A, Messori L Dalton Trans. 2018 Jul 31. doi: 10.1039/c8dt00860d. PMID:30063237<ref>PMID:30063237</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6ftv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ferroxidase]] | |||
[[Category: Human]] | |||
[[Category: Ferraro, G]] | [[Category: Ferraro, G]] | ||
[[Category: Merlino, A]] | [[Category: Merlino, A]] | ||
[[Category: Anticancer agent]] | |||
[[Category: Antimetastatic]] | |||
[[Category: Ferritin]] | |||
[[Category: Ferroxidase activity]] | |||
[[Category: Metallodrug-protein]] | |||
[[Category: Ruthenium]] | |||
[[Category: Transport protein]] | |||
Latest revision as of 11:02, 29 August 2018
X-ray structure of human heavy chain ferritin in complex with NAMI AX-ray structure of human heavy chain ferritin in complex with NAMI A
Structural highlights
Function[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). Publication Abstract from PubMedThe reaction of the antimetastatic ruthenium(iii) drug NAMI A with human H-chain ferritin (HuHf) was investigated through a variety of biophysical methods. We observed that the addition of HuHf to NAMI A solutions significantly increases the rate of spontaneous NAMI A hydrolysis suggesting the occurrence of a direct metallodrug-protein interaction. The resulting hydrolyzed Ru species binds the protein mostly forming a relatively tight 1 : 1 ruthenium/ferritin (subunit) adduct that was then separated and characterized. Notably, this adduct shows a characteristic CD spectrum in the visible region, which is diagnostic of the existence of at least one protein bound ruthenium center. The crystal structure of this NAMI A/HuHf adduct was subsequently solved at 1.58 A resolution; clear evidence is given for the selective binding of a single Ru ion to His105 of each subunit with concomitant release of all other original Ru ligands in agreement with previous observations. We also noted that NAMI A produces a partial inhibition of HuHf ferroxidase activity. The implications of the above results are discussed. The NAMI A - human ferritin system: a biophysical characterization.,Ciambellotti S, Pratesi A, Severi M, Ferraro G, Alessio E, Merlino A, Messori L Dalton Trans. 2018 Jul 31. doi: 10.1039/c8dt00860d. PMID:30063237[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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