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| | <StructureSection load='1q3x' size='340' side='right'caption='[[1q3x]], [[Resolution|resolution]] 2.23Å' scene=''> | | <StructureSection load='1q3x' size='340' side='right'caption='[[1q3x]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1q3x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q3X OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Q3X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1q3x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q3X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.23Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MASP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=1q3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q3x OCA], [http://pdbe.org/1q3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q3x RCSB], [http://www.ebi.ac.uk/pdbsum/1q3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q3x ProSAT]</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=1q3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q3x OCA], [https://pdbe.org/1q3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q3x RCSB], [https://www.ebi.ac.uk/pdbsum/1q3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q3x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN]] Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:[http://omim.org/entry/613791 613791]]. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.<ref>PMID:12904520</ref> <ref>PMID:17252003</ref> | + | [https://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN] Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:[https://omim.org/entry/613791 613791]. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.<ref>PMID:12904520</ref> <ref>PMID:17252003</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN]] Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.<ref>PMID:10946292</ref> | + | [https://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN] Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.<ref>PMID:10946292</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ambrus, G]] | + | [[Category: Ambrus G]] |
| - | [[Category: Gal, P]] | + | [[Category: Gal P]] |
| - | [[Category: Harmat, V]] | + | [[Category: Harmat V]] |
| - | [[Category: Kardos, J]] | + | [[Category: Kardos J]] |
| - | [[Category: Naray-Szabo, G]] | + | [[Category: Naray-Szabo G]] |
| - | [[Category: Szilagyi, K]] | + | [[Category: Szilagyi K]] |
| - | [[Category: Zavodszky, P]] | + | [[Category: Zavodszky P]] |
| - | [[Category: Autoactivation]]
| + | |
| - | [[Category: Complement]]
| + | |
| - | [[Category: Hinge bending]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Modular structure]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| Structural highlights
Disease
MASP2_HUMAN Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:613791. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.[1] [2]
Function
MASP2_HUMAN Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.[3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A family of serine proteases mediates the proteolytic cascades of several defense mechanisms in vertebrates, such as the complement system, blood coagulation and fibrinolysis. These proteases usually form large complexes with other glycoproteins. Their common features are their modular structures and restricted substrate specificities. The lectin pathway of complement, where mannose-binding lectin (MBL) recognizes the carbohydrate structures on pathogens, is activated by mannose-binding lectin-associated serine protease-2 (MASP-2). We present the 2.25A resolution structure of the catalytic fragment of MASP-2 encompassing the second complement control protein module (CCP2) and the serine protease (SP) domain. The CCP2 module stabilizes the structure of the SP domain as demonstrated by differential scanning calorimetry measurements. The asymmetric unit contains two molecules with different CCP-SP domain orientations, reflecting increased modular flexibility at the CCP2/SP joint. This flexibility may partly explain the ability of the MASP-2 dimer to perform all of its functions alone, whereas the same functions are mediated by the much larger C1r2-C1s2 tetramer in the C1 complex of the classical pathway. The main scaffold of the MASP-2 SP domain is chymotrypsin-like. Eight surface loops determine the S1 and other subsite specificities. Surprisingly, some surface loops of MASP-2, e.g. loop 1 and loop 2, which form the S1 pocket are similar to those of trypsin, and show significant differences if compared with those of C1s, indicating that the nearly identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions.
The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions.,Harmat V, Gal P, Kardos J, Szilagyi K, Ambrus G, Vegh B, Naray-Szabo G, Zavodszky P J Mol Biol. 2004 Oct 1;342(5):1533-46. PMID:15364579[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, Sjoholm AG, Fugger L, Jensenius JC. Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med. 2003 Aug 7;349(6):554-60. PMID:12904520 doi:http://dx.doi.org/10.1056/NEJMoa022836
- ↑ Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, Eiberg H, Gadjeva M, Ruseva M, Jensenius JC. Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 2007 Mar;8(2):154-63. Epub 2007 Jan 25. PMID:17252003 doi:10.1038/sj.gene.6364373
- ↑ Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol. 2000 Sep 1;165(5):2637-42. PMID:10946292
- ↑ Harmat V, Gal P, Kardos J, Szilagyi K, Ambrus G, Vegh B, Naray-Szabo G, Zavodszky P. The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions. J Mol Biol. 2004 Oct 1;342(5):1533-46. PMID:15364579 doi:10.1016/j.jmb.2004.07.014
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