5mt0: Difference between revisions
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==COMPLEMENT FACTOR D IN COMPLEX WITH A REVERSIBLE INDOLE CARBOXYLIC ACID BASED INHIBITOR== | ==COMPLEMENT FACTOR D IN COMPLEX WITH A REVERSIBLE INDOLE CARBOXYLIC ACID BASED INHIBITOR== | ||
<StructureSection load='5mt0' size='340' side='right' caption='[[5mt0]], [[Resolution|resolution]] 1.29Å' scene=''> | <StructureSection load='5mt0' size='340' side='right'caption='[[5mt0]], [[Resolution|resolution]] 1.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5mt0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MT0 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5mt0]] 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=5MT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MT0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QJS:5-FLUORANYL-3-[[(1~{S},2~{S})-2-PHENYLCYCLOPROPYL]CARBONYLAMINO]-1~{H}-INDOLE-2-CARBOXYLIC+ACID'>QJS</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]] 1.29Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QJS:5-FLUORANYL-3-[[(1~{S},2~{S})-2-PHENYLCYCLOPROPYL]CARBONYLAMINO]-1~{H}-INDOLE-2-CARBOXYLIC+ACID'>QJS</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5mt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mt0 OCA], [https://pdbe.org/5mt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mt0 RCSB], [https://www.ebi.ac.uk/pdbsum/5mt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mt0 ProSAT]</span></td></tr> | ||
</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 21: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 5mt0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5mt0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Complement C3 3D structures|Complement C3 3D structures]] | |||
*[[Complement factor 3D structures|Complement factor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Sweeney | [[Category: Mac Sweeney A]] | ||
[[Category: | [[Category: Ostermann N]] | ||
Latest revision as of 11:45, 9 October 2024
COMPLEMENT FACTOR D IN COMPLEX WITH A REVERSIBLE INDOLE CARBOXYLIC ACID BASED INHIBITORCOMPLEMENT FACTOR D IN COMPLEX WITH A REVERSIBLE INDOLE CARBOXYLIC ACID BASED INHIBITOR
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 PubMedChronic dysregulation of alternative complement pathway activation has been associated with diverse clinical disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinurea. Factor D is a trypsin-like serine protease with a narrow specificity for arginine in the P1 position, which catalyzes the first enzymatic reaction of the amplification loop of the alternative pathway. In this article, we describe two hit finding approaches leading to the discovery of new chemical matter for this pivotal protease of the complement system: in silico active site mapping for hot spot identification to guide rational structure-based design and NMR screening of focused and diverse fragment libraries. The wealth of information gathered by these complementary approaches enabled the identification of ligands binding to different subpockets of the latent Factor D conformation and was instrumental for understanding the binding requirements for the generation of the first known potent noncovalent reversible Factor D inhibitors. Structure-Based Library Design and Fragment Screening for the Identification of Reversible Complement Factor D Protease Inhibitors.,Vulpetti A, Randl S, Rudisser S, Ostermann N, Erbel P, Mac Sweeney A, Zoller T, Salem B, Gerhartz B, Cumin F, Hommel U, Dalvit C, Lorthiois E, Maibaum J J Med Chem. 2017 Feb 20. doi: 10.1021/acs.jmedchem.6b01684. PMID:28157311[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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