3tvj

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{{STRUCTURE_3tvj| PDB=3tvj | SCENE= }}
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==Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold==
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===Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold===
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<StructureSection load='3tvj' size='340' side='right' caption='[[3tvj]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
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{{ABSTRACT_PUBMED_22511776}}
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== Structural highlights ==
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<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>
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</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>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4djz|4djz]]</td></tr>
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<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>
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<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>
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<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>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[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> [[http://www.uniprot.org/uniprot/SGP1_SCHGR 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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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<ref>PMID:22511776</ref>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[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>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[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].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:022511776</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Mannan-binding lectin-associated serine protease-2]]
[[Category: Mannan-binding lectin-associated serine protease-2]]
[[Category: Schistocerca gregaria]]
[[Category: Schistocerca gregaria]]
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[[Category: Dobo, J.]]
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[[Category: Dobo, J]]
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[[Category: Gal, P.]]
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[[Category: Gal, P]]
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[[Category: Harmat, V.]]
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[[Category: Harmat, V]]
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[[Category: Heja, D.]]
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[[Category: Heja, D]]
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[[Category: Kekesi, K A.]]
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[[Category: Kekesi, K A]]
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[[Category: Pal, G.]]
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[[Category: Pal, G]]
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[[Category: Szasz, R.]]
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[[Category: Szasz, R]]
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[[Category: Zavodszky, P.]]
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[[Category: Zavodszky, P]]
[[Category: Allostery]]
[[Category: Allostery]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: In vitro evolution]]
[[Category: In vitro evolution]]
[[Category: Specific inhibitor]]
[[Category: Specific inhibitor]]

Revision as of 06:30, 21 December 2014

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

3tvj, resolution 1.28Å

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