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3tvj

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Revision as of 22:15, 5 August 2016

Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold

Structural highlights

3tvj is a 3 chain structure with sequence from Desert locust and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4djz
Gene:	MASP2 (HUMAN), GenBank: Y09605.1 (Desert locust)
Activity:	Mannan-binding lectin-associated serine protease-2, with EC number 3.4.21.104
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [SGP1_SCHGR] In vitro, SGPI-1/SGCI is active against alpha-chymotrypsin and trypsin while SGPI-2/SGTI is active against alpha-chymotrypsin and pancreatic elastase.

Publication Abstract from PubMed

The lectin pathway is an antibody-independent activation route of the complement system. It provides immediate defense against pathogens and altered self-cells, but it also causes severe tissue damage after stroke, heart attack and other ischemia reperfusion injuries. The pathway is triggered by target-binding of pattern recognition molecules leading to the activation of zymogen mannan-binding lectin-associated serine proteases (MASPs). MASP-2 is considered as the autonomous pathway-activator while MASP-1 as an auxiliary component. We evolved a pair of monospecific MASP inhibitors. In accordance with the key role of MASP-2, the MASP-2 inhibitor completely blocks the lectin pathway activation. Importantly, the MASP-1 inhibitor does the same demonstrating that MASP-1 is not an auxiliary but an essential pathway component. We report the first Michaelis-like complex structures of MASP-1 and MASP-2 formed with substrate-like inhibitors. The 1.28 A resolution MASP-2 structure reveals significant plasticity of the protease suggesting that either an induced fit or a conformational selection mechanism should contribute to the extreme specificity of the enzyme.

Monospecific inhibitors show that both mannan-binding lectin-associated serine protease (MASP)-1 and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2.,Heja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G J Biol Chem. 2012 Apr 16. PMID:22511776^[4]

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

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
↑ Heja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G. Monospecific inhibitors show that both mannan-binding lectin-associated serine protease (MASP)-1 and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2. J Biol Chem. 2012 Apr 16. PMID:22511776 doi:10.1074/jbc.M112.354332

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3tvj"

@@ Line 1: / Line 1: @@
 ==Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold==
 <StructureSection load='3tvj' size='340' side='right' caption='[[3tvj]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3tvj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Schistocerca_gregaria Schistocerca gregaria]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3tvj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Desert_locust Desert locust] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TVJ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4djz|4djz]]</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 Homo sapiens]), GenBank: Y09605.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7010 Schistocerca gregaria])</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]), GenBank: Y09605.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7010 Desert locust])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mannan-binding_lectin-associated_serine_protease-2 Mannan-binding lectin-associated serine protease-2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.104 3.4.21.104] </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=3tvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tvj RCSB], [http://www.ebi.ac.uk/pdbsum/3tvj PDBsum]</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=3tvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvj OCA], [http://pdbe.org/3tvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tvj RCSB], [http://www.ebi.ac.uk/pdbsum/3tvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvj ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3tvj" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Desert locust]]
+[[Category: Human]]
 [[Category: Mannan-binding lectin-associated serine protease-2]]
-[[Category: Schistocerca gregaria]]
 [[Category: Dobo, J]]
 [[Category: Gal, P]]

3tvj

From Proteopedia

Revision as of 22:15, 5 August 2016

Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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