View source for 3gov


==Crystal structure of the catalytic region of human MASP-1==
<StructureSection load='3gov' size='340' side='right'caption='[[3gov]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gov]] 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=3GOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GOV 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]] 2.55&#8491;</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></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=3gov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gov OCA], [https://pdbe.org/3gov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gov RCSB], [https://www.ebi.ac.uk/pdbsum/3gov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gov ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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> 
== 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/go/3gov_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=3gov ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 is an abundant component of the lectin pathway of complement. The related enzyme, MASP-2 is capable of activating the complement cascade alone. Though the concentration of MASP-1 far exceeds that of MASP-2, only a supporting role of MASP-1 has been identified regarding lectin pathway activation. Several non-complement substrates, like fibrinogen and factor XIII, have also been reported. MASP-1 belongs to the C1r/C1s/MASP family of modular serine proteases; however, its serine protease domain is evolutionary different. We have determined the crystal structure of the catalytic region of active MASP-1 and refined it to 2.55 A resolution. Unusual features of the structure are an internal salt bridge (similar to one in factor D) between the S1 Asp189 and Arg224, and a very long 60-loop. The functional and evolutionary differences between MASP-1 and the other members of the C1r/C1s/MASP family are reflected in the crystal structure. Structural comparison of the protease domains revealed that the substrate binding groove of MASP-1 is wide and resembles that of trypsin rather than early complement proteases explaining its relaxed specificity. Also, MASP-1's multifunctional behavior as both a complement and a coagulation enzyme is in accordance with our observation that antithrombin in the presence of heparin is a more potent inhibitor of MASP-1 than C1 inhibitor. Overall, MASP-1 behaves as a promiscuous protease. The structure shows that its substrate binding groove is accessible; however, its reactivity could be modulated by an unusually large 60-loop and an internal salt bridge involving the S1 Asp.

MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity.,Dobo J, Harmat V, Beinrohr L, Sebestyen E, Zavodszky P, Gal P J Immunol. 2009 Jul 15;183(2):1207-14. Epub 2009 Jun 29. PMID:19564340<ref>PMID:19564340</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gov" 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: Large Structures]]
[[Category: Beinrohr L]]
[[Category: Dobo J]]
[[Category: Gal P]]
[[Category: Harmat V]]
[[Category: Sebestyen E]]
[[Category: Zavodszky P]]