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4iw4

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Revision as of 09:03, 3 April 2019

Crystal structure of the serine protease domain of MASP-3 in complex with ecotin

Structural highlights

4iw4 is a 4 chain structure with sequence from Escherichia coli and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3dem
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MASP1_HUMAN] Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM: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.^[1]

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] [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.^[2] ^[3]

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^[4]

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

References

↑ Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011 Mar;43(3):197-203. doi: 10.1038/ng.757. Epub 2011 Jan 23. PMID:21258343 doi:10.1038/ng.757
↑ Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity. 2001 Jul;15(1):127-35. PMID:11485744
↑ Moller-Kristensen M, Thiel S, Sjoholm A, Matsushita M, Jensenius JC. Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. Int Immunol. 2007 Feb;19(2):141-9. Epub 2006 Dec 20. PMID:17182967 doi:dxl131
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4iw4"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the serine protease domain of MASP-3 in complex with ecotin==
-<StructureSection load='4iw4' size='340' side='right' caption='[[4iw4]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='4iw4' size='340' side='right'caption='[[4iw4]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == 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>
@@ Line 23: / Line 23: @@
 ==See Also==
 *[[Ecotin|Ecotin]]
+*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]]
 == References ==
 <references/>
@@ Line 29: / Line 30: @@
 [[Category: Escherichia coli]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gaboriaud, C]]
 [[Category: Extracellular]]

4iw4

From Proteopedia

Revision as of 09:03, 3 April 2019

Crystal structure of the serine protease domain of MASP-3 in complex with ecotin

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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