6i2x - Revision history

OCA: Redirecting to 8ayh

OCA — Wed, 21 Dec 2022 09:17:28 GMT

Redirecting to 8ayh

←Older revision		Revision as of 09:17, 21 December 2022
Line 1:		Line 1:
-		+	#REDIRECT [[8ayh]] This PDB entry is obsolete and replaced by 8ayh
-	~~==Structure of Complement C5 in Complex with small molecule inhibitor and CVF==~~	+
-	~~<StructureSection load='6i2x' size='340' side='right'caption='~~[[~~6i2x~~]]~~, [[Resolution\|resolution]] 3.35Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	<table><tr><td colspan='2'>[[6i2x]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I2X FirstGlance]. <br>	+
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i2x OCA], [http://pdbe.org/6i2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i2x RCSB], [http://www.ebi.ac.uk/pdbsum/6i2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i2x ProSAT]</span></td></tr>	+
-	~~</table>~~	+
-	~~== Disease ==~~	+
-	~~[[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[http://omim.org/~~entry/609536 609536]]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele (PubMed:15995705).	+
-	~~== Function ==~~	+
-	[[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis). [[http://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.	+
-		+
-	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>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6i2x" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	~~[[Category: Homo sapiens]]~~	+
-	~~[[Category: Large Structures]]~~	+
-	~~[[Category: Naja kaouthia]]~~	+
-	~~[[Category: Srinivas, H]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Cryo-em]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Toxin]]~~	+

OCA at 06:49, 26 June 2019

OCA — Wed, 26 Jun 2019 06:49:43 GMT

←Older revision		Revision as of 06:49, 26 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6i2x is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of Complement C5 in Complex with small molecule inhibitor and CVF==
		+	<StructureSection load='6i2x' size='340' side='right'caption='[[6i2x]], [[Resolution\|resolution]] 3.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6i2x]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I2X FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i2x OCA], [http://pdbe.org/6i2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i2x RCSB], [http://www.ebi.ac.uk/pdbsum/6i2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i2x ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[http://omim.org/entry/609536 609536]]. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele (PubMed:15995705).
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN]] Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis). [[http://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~~:	+	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~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6i2x" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Naja kaouthia]]
		+	[[Category: Srinivas, H]]
		+	[[Category: Complex]]
		+	[[Category: Cryo-em]]
		+	[[Category: Immune system]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protease]]
		+	[[Category: Toxin]]

OCA at 09:52, 13 March 2019

OCA — Wed, 13 Mar 2019 09:52:28 GMT

←Older revision		Revision as of 09:52, 13 March 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6i2x is ON HOLD	+	The entry 6i2x is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6i2x" [edit=sysop:move=sysop]

OCA — Wed, 14 Nov 2018 06:18:46 GMT

Protected "6i2x" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:18, 14 November 2018

OCA: New page: '''Unreleased structure''' The entry 6i2x is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 14 Nov 2018 06:18:45 GMT

New page: '''Unreleased structure''' The entry 6i2x is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6i2x is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]