4djz

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[[Image:4djz.png|left|200px]]
 
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{{STRUCTURE_4djz| PDB=4djz | SCENE= }}
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==Catalytic fragment of masp-1 in complex with its specific inhibitor developed by directed evolution on sgci scaffold==
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<StructureSection load='4djz' size='340' side='right'caption='[[4djz]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4djz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Schistocerca_gregaria Schistocerca gregaria]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DJZ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4djz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4djz OCA], [https://pdbe.org/4djz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4djz RCSB], [https://www.ebi.ac.uk/pdbsum/4djz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4djz ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MASP1_HUMAN MASP1_HUMAN] Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM:[https://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>
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== Function ==
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[https://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>
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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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===Catalytic fragment of masp-1 in complex with its specific inhibitor developed by directed evolution on sgci scaffold===
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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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{{ABSTRACT_PUBMED_22511776}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4djz" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[4djz]] is a 6 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=4DJZ OCA].
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*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:022511776</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[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: Fodor, K.]]
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[[Category: Fodor K]]
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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 KA]]
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[[Category: Pal, G.]]
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[[Category: Pal G]]
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[[Category: Wilmanns, M.]]
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[[Category: Wilmanns M]]
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[[Category: Zavodszky, P.]]
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[[Category: Zavodszky P]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: In vitro evolution]]
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[[Category: Specific inhibitor]]
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Current revision

Catalytic fragment of masp-1 in complex with its specific inhibitor developed by directed evolution on sgci scaffold

PDB ID 4djz

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