3tvj: Difference between revisions

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~~[[Image:3tvj.png|left|200px]]~~

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

~~The line below this paragraph, containing~~ "~~STRUCTURE_3tvj~~"~~, creates the~~ "~~Structure Box~~" on the ~~page~~.

~~You may change~~ the ~~PDB parameter (which sets~~ the ~~PDB file loaded into~~ the ~~applet)~~

== Structural highlights ==

or the ~~SCENE parameter~~ (~~which sets~~ the ~~initial scene displayed when~~ the ~~page is loaded)~~,

<table><tr><td colspan='2'>[[3tvj]] is a 3 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=3TVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVJ FirstGlance]. <br>

~~or leave~~ the ~~SCENE parameter empty for~~ the ~~default display~~.

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.28Å</td></tr>

-->

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

~~{{STRUCTURE_3tvj| PDB=3tvj | SCENE= }}~~

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvj OCA], [https://pdbe.org/3tvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvj RCSB], [https://www.ebi.ac.uk/pdbsum/3tvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvj 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>

== 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.

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

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>

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

</div>

~~<!--~~

==See Also==

~~The line below this paragraph, {{ABSTRACT_PUBMED_22511776}}, adds the Publication Abstract to the page~~

*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]]

~~(as it appears on PubMed at http://www.pubmed.gov), where 22511776 is the PubMed ID number.~~

== References ==

~~-->~~

~~{{ABSTRACT_PUBMED_22511776}}~~

__TOC__

</StructureSection>

==~~About this Structure~~==

[[~~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].

==~~Reference~~==

<~~ref group="xtra">PMID:022511776<~~/~~ref~~><~~references group="xtra"~~/>

[[Category: Homo sapiens]]

[[Category: ~~Mannan-binding lectin-associated serine protease-2~~]]

[[Category: Large Structures]]

[[Category: Schistocerca gregaria]]

[[Category: Dobo, J.]]

[[Category: Dobo J]]

[[Category: Gal, P.]]

[[Category: Gal P]]

[[Category: Harmat, V.]]

[[Category: Harmat V]]

[[Category: Heja, D.]]

[[Category: Heja D]]

[[Category: Kekesi~~, K A.~~]]

[[Category: Kekesi KA]]

[[Category: Pal, G.]]

[[Category: Pal G]]

[[Category: Szasz, R.]]

[[Category: Szasz R]]

[[Category: Zavodszky, P~~.]]~~

[[Category: Zavodszky P]]

~~[[Category: Allostery]]~~

~~[[Category: Hydrolase]]~~

~~[[Category: In vitro evolution]]~~

~~[[Category: Specific inhibitor~~]]

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@@ Line 1: / Line 1: @@
-[[Image:3tvj.png|left|200px]]
-<!--
+==Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold==
-The line below this paragraph, containing "STRUCTURE_3tvj", creates the "Structure Box" on the page.
+<StructureSection load='3tvj' size='340' side='right'caption='[[3tvj]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3tvj]] is a 3 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=3TVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TVJ FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.28&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_3tvj|  PDB=3tvj  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tvj OCA], [https://pdbe.org/3tvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tvj RCSB], [https://www.ebi.ac.uk/pdbsum/3tvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tvj 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>
+<div style="background-color:#fffaf0;">
+== 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.
-===Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold===
+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>
+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>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22511776}}, adds the Publication Abstract to the page
+*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22511776 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22511776}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[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].
-==Reference==
-<ref group="xtra">PMID:022511776</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Mannan-binding lectin-associated serine protease-2]]
+[[Category: Large Structures]]
 [[Category: Schistocerca gregaria]]
-[[Category: Dobo, J.]]
+[[Category: Dobo J]]
-[[Category: Gal, P.]]
+[[Category: Gal P]]
-[[Category: Harmat, V.]]
+[[Category: Harmat V]]
-[[Category: Heja, D.]]
+[[Category: Heja D]]
-[[Category: Kekesi, K A.]]
+[[Category: Kekesi KA]]
-[[Category: Pal, G.]]
+[[Category: Pal G]]
-[[Category: Szasz, R.]]
+[[Category: Szasz R]]
-[[Category: Zavodszky, P.]]
+[[Category: Zavodszky P]]
-[[Category: Allostery]]
-[[Category: Hydrolase]]
-[[Category: In vitro evolution]]
-[[Category: Specific inhibitor]]