1zjk: Difference between revisions
New page: left|200px<br /> <applet load="1zjk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zjk, resolution 2.18Å" /> '''Crystal structure o... |
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== | ==Crystal structure of the zymogen catalytic region of human MASP-2== | ||
Few reports have described in detail a true autoactivation process, where | <StructureSection load='1zjk' size='340' side='right'caption='[[1zjk]], [[Resolution|resolution]] 2.18Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1zjk]] is a 1 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=1ZJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZJK FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.18Å</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=1zjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zjk OCA], [https://pdbe.org/1zjk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zjk RCSB], [https://www.ebi.ac.uk/pdbsum/1zjk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zjk ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[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 == | |||
[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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zj/1zjk_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zjk ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Few reports have described in detail a true autoactivation process, where no extrinsic cleavage factors are required to initiate the autoactivation of a zymogen. Herein, we provide structural and mechanistic insight into the autoactivation of a multidomain serine protease: mannose-binding lectin-associated serine protease-2 (MASP-2), the first enzymatic component in the lectin pathway of complement activation. We characterized the proenzyme form of a MASP-2 catalytic fragment encompassing its C-terminal three domains and solved its crystal structure at 2.4 A resolution. Surprisingly, zymogen MASP-2 is capable of cleaving its natural substrate C4, with an efficiency about 10% that of active MASP-2. Comparison of the zymogen and active structures of MASP-2 reveals that, in addition to the activation domain, other loops of the serine protease domain undergo significant conformational changes. This additional flexibility could play a key role in the transition of zymogen MASP-2 into a proteolytically active form. Based on the three-dimensional structures of proenzyme and active MASP-2 catalytic fragments, we present model for the active zymogen MASP-2 complex and propose a mechanism for the autoactivation process. | |||
A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations.,Gal P, Harmat V, Kocsis A, Bian T, Barna L, Ambrus G, Vegh B, Balczer J, Sim RB, Naray-Szabo G, Zavodszky P J Biol Chem. 2005 Sep 30;280(39):33435-44. Epub 2005 Jul 21. PMID:16040602<ref>PMID:16040602</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1zjk" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Ambrus | [[Category: Ambrus G]] | ||
[[Category: Balczer | [[Category: Balczer J]] | ||
[[Category: Barna | [[Category: Barna L]] | ||
[[Category: Bian | [[Category: Bian T]] | ||
[[Category: Gal | [[Category: Gal P]] | ||
[[Category: Harmat | [[Category: Harmat V]] | ||
[[Category: Kocsis | [[Category: Kocsis A]] | ||
[[Category: Naray-Szabo | [[Category: Naray-Szabo G]] | ||
[[Category: Sim | [[Category: Sim RB]] | ||
[[Category: Vegh | [[Category: Vegh B]] | ||
[[Category: Zavodszky | [[Category: Zavodszky P]] | ||
