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| | ==Inhibiting Alternative Pathway Complement Activation by Targeting the Exosite on Factor D== | | ==Inhibiting Alternative Pathway Complement Activation by Targeting the Exosite on Factor D== |
| - | <StructureSection load='4d9q' size='340' side='right' caption='[[4d9q]], [[Resolution|resolution]] 2.28Å' scene=''> | + | <StructureSection load='4d9q' size='340' side='right'caption='[[4d9q]], [[Resolution|resolution]] 2.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4d9q]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D9Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D9Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4d9q]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D9Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D9Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.28Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d9r|4d9r]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4d9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d9q OCA], [https://pdbe.org/4d9q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d9q RCSB], [https://www.ebi.ac.uk/pdbsum/4d9q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d9q ProSAT]</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=4d9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d9q OCA], [http://pdbe.org/4d9q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d9q RCSB], [http://www.ebi.ac.uk/pdbsum/4d9q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d9q ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/F6YBP7_MACMU F6YBP7_MACMU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Macmu]] | + | [[Category: Large Structures]] |
| - | [[Category: Murray, J M]] | + | [[Category: Macaca mulatta]] |
| - | [[Category: Wiesmann, C]] | + | [[Category: Murray JM]] |
| - | [[Category: Antibody]] | + | [[Category: Wiesmann C]] |
| - | [[Category: Chymotrypsin]]
| + | |
| - | [[Category: Complement]]
| + | |
| - | [[Category: Exosite]]
| + | |
| - | [[Category: Fab]]
| + | |
| - | [[Category: Factor d]]
| + | |
| - | [[Category: Hydrolase-immune system complex]]
| + | |
| - | [[Category: Protease]]
| + | |
| Structural highlights
Function
F6YBP7_MACMU
Publication Abstract from PubMed
The alternative complement pathway, by virtue of its amplifying property, has been implicated in a number of inflammatory diseases and constitutes an attractive therapeutic target. An anti-factor D Fab fragment (AFD) was generated to inhibit the alternative complement pathway in advanced dry age-related macular degeneration. AFD potently prevented factor D (FD)-mediated proteolytic activation of its macro-molecular substrate C3bB, but not proteolysis of a small synthetic substrate, indicating that AFD did not block access of substrate to the catalytic site. The crystal structures of AFD in complex with human and cynomolgus FD (at 2.4 A and 2.3 A, respectively) revealed the molecular details of the inhibitory mechanism. The structures showed that the AFD binding site included surface loops of FD that form part of the C3bB exosite. Thus, AFD inhibited FD proteolytic function by interfering with macromolecular substrate access rather than by inhibiting FD catalysis, providing the molecular basis of AFD-mediated inhibition of a rate-limiting step in the alternative complement pathway.
Inhibiting alternative pathway complement activation by targeting the exosite of factor D.,Katschke KJ, Wu P, Ganesan R, Kelley RF, Mathieu MA, Hass PE, Murray J, Kirchhofer D, Wiesmann C, van Lookeren Campagne M J Biol Chem. 2012 Feb 23. PMID:22362762[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Katschke KJ, Wu P, Ganesan R, Kelley RF, Mathieu MA, Hass PE, Murray J, Kirchhofer D, Wiesmann C, van Lookeren Campagne M. Inhibiting alternative pathway complement activation by targeting the exosite of factor D. J Biol Chem. 2012 Feb 23. PMID:22362762 doi:10.1074/jbc.M112.345082
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