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4d9r

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Revision as of 21:54, 5 August 2016

Inhibiting Alternative Pathway Complement Activation by Targeting the Exosite on Factor D

Structural highlights

4d9r is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4d9q
Gene:	CFD, DF, Factor D, PFD (HUMAN), IGKC (HUMAN), IGHG1 (HUMAN)
Activity:	Complement factor D, with EC number 3.4.21.46
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4d9r"

@@ Line 1: / Line 1: @@
 ==Inhibiting Alternative Pathway Complement Activation by Targeting the Exosite on Factor D==
 <StructureSection load='4d9r' size='340' side='right' caption='[[4d9r]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4d9r]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D9R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D9R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4d9r]] is a 6 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=4D9R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D9R FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d9q|4d9q]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CFD, DF, Factor D, PFD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IGKC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CFD, DF, Factor D, PFD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGKC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d9r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d9r RCSB], [http://www.ebi.ac.uk/pdbsum/4d9r PDBsum]</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=4d9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d9r OCA], [http://pdbe.org/4d9r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d9r RCSB], [http://www.ebi.ac.uk/pdbsum/4d9r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d9r ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4d9r" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 26: / Line 28: @@
 </StructureSection>
 [[Category: Complement factor D]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Murray, J M]]
 [[Category: Wiesmann, C]]

4d9r

From Proteopedia

Revision as of 21:54, 5 August 2016

Inhibiting Alternative Pathway Complement Activation by Targeting the Exosite on Factor D

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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