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| | <StructureSection load='5ubm' size='340' side='right'caption='[[5ubm]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='5ubm' size='340' side='right'caption='[[5ubm]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ubm]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Amazon_leech Amazon leech] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UBM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UBM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ubm]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Haementeria_ghilianii Haementeria ghilianii] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UBM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Complement_subcomponent_C1s Complement subcomponent C1s], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.42 3.4.21.42] </span></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=5ubm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ubm OCA], [https://pdbe.org/5ubm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ubm RCSB], [https://www.ebi.ac.uk/pdbsum/5ubm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ubm ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ubm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ubm OCA], [http://pdbe.org/5ubm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ubm RCSB], [http://www.ebi.ac.uk/pdbsum/5ubm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ubm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN]] Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:[http://omim.org/entry/613783 613783]]. A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. | + | [https://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN] Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:[https://omim.org/entry/613783 613783]. A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN]] C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4. | + | [https://www.uniprot.org/uniprot/C1S_HUMAN C1S_HUMAN] C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Amazon leech]] | + | [[Category: Haementeria ghilianii]] |
| - | [[Category: Complement subcomponent C1s]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pang, S S]] | + | [[Category: Pang SS]] |
| - | [[Category: Whisstock, J C]] | + | [[Category: Whisstock JC]] |
| - | [[Category: Complement system c1s protease inhibitor complex]]
| + | |
| - | [[Category: Immune system-inhibitor complex]]
| + | |
| Structural highlights
Disease
C1S_HUMAN Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:613783. A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.
Function
C1S_HUMAN C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.
Publication Abstract from PubMed
Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. Complement is activated by three pathways: classical, lectin, and alternative. The classical and lectin pathways are initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases. Given the role of complement in disease, there is a requirement for inhibitors to control the initiating proteases. In this article, we show that a novel inhibitor, gigastasin, from the giant Amazon leech, potently inhibits C1s and MASP-2, whereas it is also a good inhibitor of MASP-1. Gigastasin is a poor inhibitor of C1r. The inhibitor blocks the active sites of C1s and MASP-2, as well as the anion-binding exosites of the enzymes via sulfotyrosine residues. Complement deposition assays revealed that gigastasin is an effective inhibitor of complement activation in vivo, especially for activation via the lectin pathway. These data suggest that the cumulative effects of inhibiting both MASP-2 and MASP-1 have a greater effect on the lectin pathway than the more potent inhibition of only C1s of the classical pathway.
The Structural Basis for Complement Inhibition by Gigastasin, a Protease Inhibitor from the Giant Amazon Leech.,Pang SS, Wijeyewickrema LC, Hor L, Tan S, Lameignere E, Conway EM, Blom AM, Mohlin FC, Liu X, Payne RJ, Whisstock JC, Pike RN J Immunol. 2017 Oct 23. pii: ji1700158. doi: 10.4049/jimmunol.1700158. PMID:29061764[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pang SS, Wijeyewickrema LC, Hor L, Tan S, Lameignere E, Conway EM, Blom AM, Mohlin FC, Liu X, Payne RJ, Whisstock JC, Pike RN. The Structural Basis for Complement Inhibition by Gigastasin, a Protease Inhibitor from the Giant Amazon Leech. J Immunol. 2017 Oct 23. pii: ji1700158. doi: 10.4049/jimmunol.1700158. PMID:29061764 doi:http://dx.doi.org/10.4049/jimmunol.1700158
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