5fck: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='5fck' size='340' side='right'caption='[[5fck]], [[Resolution|resolution]] 1.86Å' scene=''> | <StructureSection load='5fck' size='340' side='right'caption='[[5fck]], [[Resolution|resolution]] 1.86Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fck]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5fck]] is a 1 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=5FCK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FCK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5WC:1-[2-[(1~{R},3~{S},5~{R})-3-[[(1~{R})-1-(3-CHLORANYL-2-FLUORANYL-PHENYL)ETHYL]CARBAMOYL]-2-AZABICYCLO[3.1.0]HEXAN-2-YL]-2-OXIDANYLIDENE-ETHYL]PYRAZOLO[3,4-C]PYRIDINE-3-CARBOXAMIDE'>5WC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.86Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5WC:1-[2-[(1~{R},3~{S},5~{R})-3-[[(1~{R})-1-(3-CHLORANYL-2-FLUORANYL-PHENYL)ETHYL]CARBAMOYL]-2-AZABICYCLO[3.1.0]HEXAN-2-YL]-2-OXIDANYLIDENE-ETHYL]PYRAZOLO[3,4-C]PYRIDINE-3-CARBOXAMIDE'>5WC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5fck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fck OCA], [https://pdbe.org/5fck PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fck RCSB], [https://www.ebi.ac.uk/pdbsum/5fck PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fck ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/CFAD_HUMAN CFAD_HUMAN] Defects in CFD are the cause of complement factor D deficiency (CFDD) [MIM:[https://omim.org/entry/613912 613912]. CFDD is an immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/CFAD_HUMAN CFAD_HUMAN] Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 31: | Line 30: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Sweeney | [[Category: Mac Sweeney A]] | ||
Latest revision as of 09:46, 19 July 2023
COMPLEMENT FACTOR D IN COMPLEX WITH COMPOUND 5COMPLEMENT FACTOR D IN COMPLEX WITH COMPOUND 5
Structural highlights
DiseaseCFAD_HUMAN Defects in CFD are the cause of complement factor D deficiency (CFDD) [MIM:613912. CFDD is an immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. FunctionCFAD_HUMAN Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway. Publication Abstract from PubMedComplement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways. The protease factor D (FD) is essential for this amplification process, which, when dysregulated, predisposes individuals to diverse disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinuria (PNH). Here we describe the identification of potent and selective small-molecule inhibitors of FD. These inhibitors efficiently block alternative pathway (AP) activation and prevent both C3 deposition onto, and lysis of, PNH erythrocytes. Their oral administration inhibited lipopolysaccharide-induced AP activation in FD-humanized mice. These data demonstrate the feasibility of inhibiting the AP with small-molecule antagonists and support the development of FD inhibitors for the treatment of complement-mediated diseases. Small-molecule factor D inhibitors targeting the alternative complement pathway.,Maibaum J, Liao SM, Vulpetti A, Ostermann N, Randl S, Rudisser S, Lorthiois E, Erbel P, Kinzel B, Kolb FA, Barbieri S, Wagner J, Durand C, Fettis K, Dussauge S, Hughes N, Delgado O, Hommel U, Gould T, Sweeney AM, Gerhartz B, Cumin F, Flohr S, Schubart A, Jaffee B, Harrison R, Risitano AM, Eder J, Anderson K Nat Chem Biol. 2016 Oct 24. doi: 10.1038/nchembio.2208. PMID:27775713[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References
|
| ||||||||||||||||||