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1cfa

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[[Image:1cfa.gif|left|200px]]
 
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{{Structure
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==SOLUTION STRUCTURE OF A SEMI-SYNTHETIC C5A RECEPTOR ANTAGONIST AT PH 5.2, 303K, NMR, 20 STRUCTURES==
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|PDB= 1cfa |SIZE=350|CAPTION= <scene name='initialview01'>1cfa</scene>
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<StructureSection load='1cfa' size='340' side='right'caption='[[1cfa]]' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1cfa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CFA FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAR:D-ARGININE'>DAR</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cfa OCA], [https://pdbe.org/1cfa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cfa RCSB], [https://www.ebi.ac.uk/pdbsum/1cfa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cfa ProSAT]</span></td></tr>
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</table>
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'''SOLUTION STRUCTURE OF A SEMI-SYNTHETIC C5A RECEPTOR ANTAGONIST AT PH 5.2, 303K, NMR, 20 STRUCTURES'''
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== Disease ==
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[https://www.uniprot.org/uniprot/CO5_HUMAN CO5_HUMAN] Defects in C5 are the cause of complement component 5 deficiency (C5D) [MIM:[https://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).
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== Function ==
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==Overview==
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[https://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).
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The tertiary structure of a unique C5a receptor antagonist was determined by two-dimensional NMR spectroscopy. The core domain of this 8-kDa antagonist exists as an antiparallel helical bundle, similar to recombinant human (rh)-C5a. However, unlike C5a, the antagonist's C terminus was found to be conformationally restricted along a groove between helices one and four in the core domain. This conformational restriction situates C-terminal D-Arg 75 in a wedge between core residues Arg 46 and His 15. Correlation of the antagonist's tertiary structure with point mutation analysis revealed the formation of a positively charged contiguous contact surface comprised of D-Arg 75, Arg 46, Lys 49, and His 15. The significance of this surface in generating antagonist properties implies a single binding site with the C5a receptor and provides a structural template for drug design.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Disease==
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Check<jmol>
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Known disease associated with this structure: C5 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120900 120900]]
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cf/1cfa_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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1CFA is a [[Single protein]] structure of 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=1CFA OCA].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1cfa ConSurf].
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Solution structure of a unique C5a semi-synthetic antagonist: implications in receptor binding., Zhang X, Boyar W, Galakatos N, Gonnella NC, Protein Sci. 1997 Jan;6(1):65-72. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9007977 9007977]
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Boyar, W.]]
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[[Category: Boyar W]]
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[[Category: Galakatos, N.]]
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[[Category: Galakatos N]]
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[[Category: Gonnella, N C.]]
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[[Category: Gonnella NC]]
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[[Category: Zhang, X.]]
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[[Category: Zhang X]]
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[[Category: aggregation inhibitor]]
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[[Category: complement alternate pathway]]
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[[Category: complement factor]]
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[[Category: complex (complement factor/peptide)]]
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[[Category: glycoprotein]]
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[[Category: gp antagonist]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:23:40 2008''
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Current revision

SOLUTION STRUCTURE OF A SEMI-SYNTHETIC C5A RECEPTOR ANTAGONIST AT PH 5.2, 303K, NMR, 20 STRUCTURES

PDB ID 1cfa

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