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| | <StructureSection load='4iw4' size='340' side='right'caption='[[4iw4]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='4iw4' size='340' side='right'caption='[[4iw4]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iw4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IW4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IW4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iw4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=4IW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IW4 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dem|3dem]]</td></tr> | + | </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=4iw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iw4 OCA], [https://pdbe.org/4iw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iw4 RCSB], [https://www.ebi.ac.uk/pdbsum/4iw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iw4 ProSAT]</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=4iw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iw4 OCA], [http://pdbe.org/4iw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iw4 RCSB], [http://www.ebi.ac.uk/pdbsum/4iw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iw4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/MASP1_HUMAN MASP1_HUMAN]] Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM:[http://omim.org/entry/257920 257920]]. 3MC1 is a disorder characterized by facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes.<ref>PMID:21258343</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ECOT_ECOLI ECOT_ECOLI]] General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706] [[http://www.uniprot.org/uniprot/MASP1_HUMAN MASP1_HUMAN]] Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5.<ref>PMID:11485744</ref> <ref>PMID:17182967</ref> | + | [https://www.uniprot.org/uniprot/ECOT_ECOLI ECOT_ECOLI] General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gaboriaud, C]] | + | [[Category: Gaboriaud C]] |
| - | [[Category: Extracellular]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Protease]]
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| - | [[Category: Trypsin-like fold]]
| + | |
| Structural highlights
Function
ECOT_ECOLI General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706]
Publication Abstract from PubMed
Mannan-binding lectin (MBL), ficolins and collectin-11 are known to associate with three homologous modular proteases, the MBL-Associated Serine Proteases (MASPs). The crystal structures of the catalytic domains of MASP-1 and MASP-2 have been solved, but the structure of the corresponding domain of MASP-3 remains unknown. A link between mutations in the MASP1/3 gene and the rare autosomal recessive 3MC (Mingarelli, Malpuech, Michels and Carnevale,) syndrome, characterized by various developmental disorders, was discovered recently, revealing an unexpected important role of MASP-3 in early developmental processes. To gain a first insight into the enzymatic and structural properties of MASP-3, a recombinant form of its serine protease (SP) domain was produced and characterized. The amidolytic activity of this domain on fluorescent peptidyl-aminomethylcoumarin substrates was shown to be considerably lower than that of other members of the C1r/C1s/MASP family. The E. coli protease inhibitor ecotin bound to the SP domains of MASP-3 and MASP-2, whereas no significant interaction was detected with MASP-1, C1r and C1s. A tetrameric complex comprising an ecotin dimer and two MASP-3 SP domains was isolated and its crystal structure was solved and refined to 3.2 A. Analysis of the ecotin/MASP-3 interfaces allows a better understanding of the differential reactivity of the C1r/C1s/MASP protease family members towards ecotin, and comparison of the MASP-3 SP domain structure with those of other trypsin-like proteases yields novel hypotheses accounting for its zymogen-like properties in vitro.
The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin.,Gaboriaud C, Gupta RK, Martin L, Lacroix M, Serre L, Teillet F, Arlaud GJ, Rossi V, Thielens NM PLoS One. 2013 Jul 4;8(7):e67962. doi: 10.1371/journal.pone.0067962. Print 2013. PMID:23861840[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gaboriaud C, Gupta RK, Martin L, Lacroix M, Serre L, Teillet F, Arlaud GJ, Rossi V, Thielens NM. The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. PLoS One. 2013 Jul 4;8(7):e67962. doi: 10.1371/journal.pone.0067962. Print 2013. PMID:23861840 doi:10.1371/journal.pone.0067962
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