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| | <StructureSection load='4cbn' size='340' side='right'caption='[[4cbn]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4cbn' size='340' side='right'caption='[[4cbn]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cbn]] is a 2 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=4CBN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CBN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cbn]] is a 2 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=4CBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CBN 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></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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cbo|4cbo]]</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></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Complement_factor_D Complement factor D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.46 3.4.21.46] </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=4cbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbn OCA], [https://pdbe.org/4cbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cbn RCSB], [https://www.ebi.ac.uk/pdbsum/4cbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbn 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=4cbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbn OCA], [http://pdbe.org/4cbn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cbn RCSB], [http://www.ebi.ac.uk/pdbsum/4cbn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CFAD_HUMAN CFAD_HUMAN]] Defects in CFD are the cause of complement factor D deficiency (CFDD) [MIM:[http://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. | + | [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 == |
| - | [[http://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. | + | [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 == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Complement factor D]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Burnley, B T]] | + | [[Category: Burnley BT]] |
| - | [[Category: Forneris, F]] | + | [[Category: Forneris F]] |
| - | [[Category: Gros, P]] | + | [[Category: Gros P]] |
| - | [[Category: Complement system]]
| + | |
| - | [[Category: Ensemble refinement]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Disease
CFAD_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.
Function
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.
Publication Abstract from PubMed
Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or `exosite', region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na(+) and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na(+) ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail.
Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D.,Forneris F, Burnley BT, Gros P Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):733-43. doi:, 10.1107/S1399004713032549. Epub 2014 Feb 15. PMID:24598742[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Forneris F, Burnley BT, Gros P. Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D. Acta Crystallogr D Biol Crystallogr. 2014 Mar;70(Pt 3):733-43. doi:, 10.1107/S1399004713032549. Epub 2014 Feb 15. PMID:24598742 doi:http://dx.doi.org/10.1107/S1399004713032549
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