8ayh

From Proteopedia

(Difference between revisions)

Current revision

Structure of Complement C5 in Complex with small molecule inhibitor and CVF

Structural highlights

8ayh is a 3 chain structure with sequence from Homo sapiens and Naja kaouthia. This structure supersedes the now removed PDB entry 6i2x. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VCO3_NAJKA Complement-activating protein in cobra venom. It is a structural and functional analog of complement component C3b, the activated form of C3. It binds factor B (CFB), which is subsequently cleaved by factor D (CFD) to form the bimolecular complex CVF/Bb. CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. Structurally, it resembles the C3b degradation product C3c, which is not able to form a C3/C5 convertase. Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions of complement regulatory factors H (CFH) and I (CFI). Therefore, CVF continuously activates complement resulting in the depletion of complement activity.

Publication Abstract from PubMed

The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.

A small-molecule inhibitor of C5 complement protein.,Jendza K, Kato M, Salcius M, Srinivas H, De Erkenez A, Nguyen A, McLaughlin D, Be C, Wiesmann C, Murphy J, Bolduc P, Mogi M, Duca J, Namil A, Capparelli M, Darsigny V, Meredith E, Tichkule R, Ferrara L, Heyder J, Liu F, Horton PA, Romanowski MJ, Schirle M, Mainolfi N, Anderson K, Michaud GA Nat Chem Biol. 2019 Jul;15(7):666-668. doi: 10.1038/s41589-019-0303-9. Epub 2019 , Jun 17. PMID:31209353^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jendza K, Kato M, Salcius M, Srinivas H, De Erkenez A, Nguyen A, McLaughlin D, Be C, Wiesmann C, Murphy J, Bolduc P, Mogi M, Duca J, Namil A, Capparelli M, Darsigny V, Meredith E, Tichkule R, Ferrara L, Heyder J, Liu F, Horton PA, Romanowski MJ, Schirle M, Mainolfi N, Anderson K, Michaud GA. A small-molecule inhibitor of C5 complement protein. Nat Chem Biol. 2019 Jul;15(7):666-668. doi: 10.1038/s41589-019-0303-9. Epub 2019 , Jun 17. PMID:31209353 doi:http://dx.doi.org/10.1038/s41589-019-0303-9

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8ayh"

Categories: Homo sapiens | Large Structures | Naja kaouthia | Srinivas H

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ayh is ON HOLD
+==Structure of Complement C5 in Complex with small molecule inhibitor and CVF==
+<StructureSection load='8ayh' size='340' side='right'caption='[[8ayh]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ayh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6i2x 6i2x]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AYH FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H1H:5-methoxy-2-[[(1~{S})-1-(2-methoxyphenyl)ethyl]carbamoylamino]-4-(4-methylpentoxy)benzoic+acid'>H1H</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8ayh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ayh OCA], [https://pdbe.org/8ayh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ayh RCSB], [https://www.ebi.ac.uk/pdbsum/8ayh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ayh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/VCO3_NAJKA VCO3_NAJKA] Complement-activating protein in cobra venom. It is a structural and functional analog of complement component C3b, the activated form of C3. It binds factor B (CFB), which is subsequently cleaved by factor D (CFD) to form the bimolecular complex CVF/Bb. CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. Structurally, it resembles the C3b degradation product C3c, which is not able to form a C3/C5 convertase. Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions of complement regulatory factors H (CFH) and I (CFI). Therefore, CVF continuously activates complement resulting in the depletion of complement activity.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.
-Authors: Srinivas, H.
+A small-molecule inhibitor of C5 complement protein.,Jendza K, Kato M, Salcius M, Srinivas H, De Erkenez A, Nguyen A, McLaughlin D, Be C, Wiesmann C, Murphy J, Bolduc P, Mogi M, Duca J, Namil A, Capparelli M, Darsigny V, Meredith E, Tichkule R, Ferrara L, Heyder J, Liu F, Horton PA, Romanowski MJ, Schirle M, Mainolfi N, Anderson K, Michaud GA Nat Chem Biol. 2019 Jul;15(7):666-668. doi: 10.1038/s41589-019-0303-9. Epub 2019 , Jun 17. PMID:31209353<ref>PMID:31209353</ref>
-Description: Structure of Complement C5 in Complex with small molecule inhibitor and CVF
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Srinivas, H]]
+<div class="pdbe-citations 8ayh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Naja kaouthia]]
+[[Category: Srinivas H]]

8ayh

From Proteopedia

Current revision

Structure of Complement C5 in Complex with small molecule inhibitor and CVF

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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