This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3tvj

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:40, 14 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold==
==Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold==
-
<StructureSection load='3tvj' size='340' side='right' caption='[[3tvj]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
+
<StructureSection load='3tvj' size='340' side='right'caption='[[3tvj]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<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>
+
<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>
-
</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>
+
</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4djz|4djz]]</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>
-
<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>
+
<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>
-
<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>
+
-
<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>
+
</table>
</table>
== Disease ==
== Disease ==
-
[[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>
+
[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 ==
== Function ==
-
[[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.
+
[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.
+
-
 
+
-
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>
+
==See Also==
-
</div>
+
*[[Mannan-binding lectin serine protease|Mannan-binding lectin serine protease]]
== References ==
== References ==
<references/>
<references/>
Line 26: Line 20:
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Mannan-binding lectin-associated serine protease-2]]
+
[[Category: Large Structures]]
[[Category: Schistocerca gregaria]]
[[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]]
+

Current revision

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

PDB ID 3tvj

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3tvj"
Personal tools