View source for 3kan


==D-dopachrome tautomerase (D-DT)/macrophage migration inhibitory factor 2 (MIF2) complexed with inhibitor 4-IPP==
<StructureSection load='3kan' size='340' side='right'caption='[[3kan]], [[Resolution|resolution]] 1.13&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3kan]] is a 3 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=3KAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KAN 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]] 1.13&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=RW1:4-PHENYLPYRIMIDINE'>RW1</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=3kan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kan OCA], [https://pdbe.org/3kan PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kan RCSB], [https://www.ebi.ac.uk/pdbsum/3kan PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kan ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/DOPD_HUMAN DOPD_HUMAN] Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI).
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== Publication Abstract from PubMed ==
We report a new inflammatory activity for extracellular d-dopachrome tautomerase (D-DT), the recruitment of neutrophils to the lung on D-DT intratracheal installation of C57BL/6J mice with an EC50 of 5.6 mug. We also find that D-DT and macrophage migration inhibitory factor (MIF) have additive effects in neutrophil recruitment. Although the tautomerase site of D-DT and its homologue MIF are biophysically very different, 4-iodo-6-phenylpyrimidine (4-IPP) forms a covalent bond with Pro-1 of both proteins, resulting in a 6-phenylpyrimidine (6-PP) adduct. Recruitment of neutrophils to the lung for the 6-PP adducts of D-DT and MIF are reduced by approximately 50% relative to the apo proteins, demonstrating that an unmodified Pro-1 is important for this activity, but there is no cooperativity in inhibition of the proteins together. The differences in the binding mode of the 6-PP adduct for D-DT was determined by crystallographic studies at 1.13 A resolution and compared to the structure of the MIF-6-PP complex. There are major differences in the location of the 6-PP adduct to the D-DT and MIF active sites that provide insight into the lack of cooperativity by 4-IPP and into tuning the properties of the covalent inhibitors of D-DT and MIF that are necessary for the development of therapeutic small molecules against neutrophil damage from lung infections such as Pseudomonas aeruginosa in cystic fibrosis and immunocompromised patients.-Rajasekaran, D., Zierow, S., Syed, M., Bucala, R., Bhandari, V., Lolis, E. J. Targeting distinct tautomerase sites of D-DT and MIF with a single molecule for inhibition of neutrophil lung recruitment.

Targeting distinct tautomerase sites of D-DT and MIF with a single molecule for inhibition of neutrophil lung recruitment.,Rajasekaran D, Zierow S, Syed M, Bucala R, Bhandari V, Lolis EJ FASEB J. 2014 Jul 11. pii: fj.14-256636. PMID:25016026<ref>PMID:25016026</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 3kan" style="background-color:#fffaf0;"></div>

==See Also==
*[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lolis E]]
[[Category: Zierow S]]