1gcz
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 3: | Line 3: | ||
<StructureSection load='1gcz' size='340' side='right'caption='[[1gcz]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='1gcz' size='340' side='right'caption='[[1gcz]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1gcz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[1gcz]] 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=1GCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GCZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YZ9:7-HYDROXY-2-OXO-CHROMENE-3-CARBOXYLIC+ACID+ETHYL+ESTER'>YZ9</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YZ9:7-HYDROXY-2-OXO-CHROMENE-3-CARBOXYLIC+ACID+ETHYL+ESTER'>YZ9</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=1gcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gcz OCA], [https://pdbe.org/1gcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gcz RCSB], [https://www.ebi.ac.uk/pdbsum/1gcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gcz 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=1gcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gcz OCA], [https://pdbe.org/1gcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gcz RCSB], [https://www.ebi.ac.uk/pdbsum/1gcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gcz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | + | [https://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN] Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[https://omim.org/entry/604302 604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. | |
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN] Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.<ref>PMID:15908412</ref> <ref>PMID:17443469</ref> | |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 22: | Line 22: | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gcz ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gcz ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine released from T-cells and macrophages. Although a detailed understanding of the biological functions of MIF has not yet been clarified, it is known that MIF catalyzes the tautomerization of a nonphysiological molecule, D-dopachrome. Using a structure-based computer-assisted search of two databases of commercially available compounds, we have found 14 novel tautomerase inhibitors of MIF whose K(i) values are in the range of 0.038-7.4 microM. We also have determined the crystal structure of MIF complexed with the hit compound 1. It showed that the hit compound is located in the active site of MIF containing the N-terminal proline which plays an important role in the tautomerase reaction and forms several hydrogen bonds and undergoes hydrophobic interactions. A crystallographic study also revealed that there is a hydrophobic surface which consists of Pro-33, Tyr-36, Trp-108, and Phe-113 at the rim of the active site of MIF, and molecular modeling studies indicated that several more potent hit compounds have the aromatic rings which can interact with this hydrophobic surface. To our knowledge, our compounds are the most potent tautomerase inhibitors of MIF. One of these small, drug-like molecules has been cocrystallized with MIF and binds to the active site for tautomerase activity. Molecular modeling also suggests that the other hit compounds can bind in a similar fashion. | ||
| - | |||
| - | Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography.,Orita M, Yamamoto S, Katayama N, Aoki M, Takayama K, Yamagiwa Y, Seki N, Suzuki H, Kurihara H, Sakashita H, Takeuchi M, Fujita S, Yamada T, Tanaka A J Med Chem. 2001 Feb 15;44(4):540-7. PMID:11170644<ref>PMID:11170644</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1gcz" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| Line 38: | Line 29: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Katayama | + | [[Category: Katayama N]] |
| - | [[Category: Kurihara | + | [[Category: Kurihara H]] |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) COMPLEXED WITH INHIBITOR.
| |||||||||||
