4djz

From Proteopedia

(Difference between revisions)

Revision as of 09:22, 5 August 2016

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

Structural highlights

4djz is a 6 chain structure with sequence from Desert locust and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3tvj
Gene:	CRARF, CRARF1, MASP1, PRSS5 (HUMAN), Y09605.1 (Desert locust)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MASP1_HUMAN] Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM: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.^[1]

Function

[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.^[2] ^[3] [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.

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^[4]

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

References

↑ Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet. 2011 Mar;43(3):197-203. doi: 10.1038/ng.757. Epub 2011 Jan 23. PMID:21258343 doi:10.1038/ng.757
↑ Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity. 2001 Jul;15(1):127-35. PMID:11485744
↑ Moller-Kristensen M, Thiel S, Sjoholm A, Matsushita M, Jensenius JC. Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. Int Immunol. 2007 Feb;19(2):141-9. Epub 2006 Dec 20. PMID:17182967 doi:dxl131
↑ Heja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G. 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. J Biol Chem. 2012 Apr 16. PMID:22511776 doi:10.1074/jbc.M112.354332

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4djz"

@@ Line 1: / Line 1: @@
 ==Catalytic fragment of masp-1 in complex with its specific inhibitor developed by directed evolution on sgci scaffold==
 <StructureSection load='4djz' size='340' side='right' caption='[[4djz]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DJZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4djz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Desert_locust Desert locust] and [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DJZ FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tvj|3tvj]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CRARF, CRARF1, MASP1, PRSS5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), Y09605.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7010 Schistocerca gregaria])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CRARF, CRARF1, MASP1, PRSS5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Y09605.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7010 Desert locust])</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=4djz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4djz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4djz RCSB], [http://www.ebi.ac.uk/pdbsum/4djz PDBsum]</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=4djz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4djz OCA], [http://pdbe.org/4djz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4djz RCSB], [http://www.ebi.ac.uk/pdbsum/4djz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4djz ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4djz" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Desert locust]]
-[[Category: Schistocerca gregaria]]
+[[Category: Human]]
 [[Category: Dobo, J]]
 [[Category: Fodor, K]]

4djz

From Proteopedia

Revision as of 09:22, 5 August 2016

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

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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