6fuh: Difference between revisions
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==Complement factor D in complex with the inhibitor (4-((3-(aminomethyl)phenyl)amino)quinazolin-2-yl)-L-valine== | |||
<StructureSection load='6fuh' size='340' side='right' caption='[[6fuh]], [[Resolution|resolution]] 1.37Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fuh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FUH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FUH FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E88:(2~{S})-2-[[4-[[3-(aminomethyl)phenyl]amino]quinazolin-2-yl]amino]-3-methyl-butanoic+acid'>E88</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fug|6fug]]</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=6fuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fuh OCA], [http://pdbe.org/6fuh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fuh RCSB], [http://www.ebi.ac.uk/pdbsum/6fuh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fuh ProSAT]</span></td></tr> | |||
</table> | |||
== 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. | |||
== 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Complement Factor D, a serine protease of the S1 family and key component of the alternative pathway amplification loop, represents a promising target for the treatment of several prevalent and rare diseases linked to the innate immune system. Previously reported FD inhibitors have been shown to bind to the FD active site in its self-inhibited conformation characterized by the presence of a salt bridge at the bottom of the S1 pocket between Asp189 and Arg218. We report herein a new set of small-molecule FD ligands that harbor a basic S1 binding moiety directly binding to the carboxylate of Asp189, thereby displacing the Asp189-Arg218 ionic interaction and significantly changing the conformation of the self-inhibitory loop. | |||
Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D.,Vulpetti A, Ostermann N, Randl S, Yoon T, Mac Sweeney A, Cumin F, Lorthiois E, Rudisser S, Erbel P, Maibaum J ACS Med Chem Lett. 2018 Apr 24;9(5):490-495. doi: 10.1021/acsmedchemlett.8b00104., eCollection 2018 May 10. PMID:29795765<ref>PMID:29795765</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6fuh" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Complement factor D]] | |||
[[Category: Erbel, P]] | |||
[[Category: Lorthiois, E]] | [[Category: Lorthiois, E]] | ||
[[Category: Maibaum, J]] | [[Category: Maibaum, J]] | ||
[[Category: Ostermann, N]] | [[Category: Ostermann, N]] | ||
[[Category: | [[Category: Randl, S]] | ||
[[Category: Ruedisser, S]] | |||
[[Category: Sweeney, A Mac]] | |||
[[Category: Vulpetti, A]] | [[Category: Vulpetti, A]] | ||
[[Category: Yoon, T]] | [[Category: Yoon, T]] | ||
[[Category: | [[Category: Complex]] | ||
[[Category: | [[Category: Hydrolase]] | ||
[[Category: | [[Category: Inhibitor]] | ||
[[Category: Serine protease]] | |||
Revision as of 09:01, 6 June 2018
Complement factor D in complex with the inhibitor (4-((3-(aminomethyl)phenyl)amino)quinazolin-2-yl)-L-valineComplement factor D in complex with the inhibitor (4-((3-(aminomethyl)phenyl)amino)quinazolin-2-yl)-L-valine
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 PubMedComplement Factor D, a serine protease of the S1 family and key component of the alternative pathway amplification loop, represents a promising target for the treatment of several prevalent and rare diseases linked to the innate immune system. Previously reported FD inhibitors have been shown to bind to the FD active site in its self-inhibited conformation characterized by the presence of a salt bridge at the bottom of the S1 pocket between Asp189 and Arg218. We report herein a new set of small-molecule FD ligands that harbor a basic S1 binding moiety directly binding to the carboxylate of Asp189, thereby displacing the Asp189-Arg218 ionic interaction and significantly changing the conformation of the self-inhibitory loop. Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D.,Vulpetti A, Ostermann N, Randl S, Yoon T, Mac Sweeney A, Cumin F, Lorthiois E, Rudisser S, Erbel P, Maibaum J ACS Med Chem Lett. 2018 Apr 24;9(5):490-495. doi: 10.1021/acsmedchemlett.8b00104., eCollection 2018 May 10. PMID:29795765[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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