1zjk

From Proteopedia

(Difference between revisions)

Revision as of 10:09, 8 January 2015

Crystal structure of the zymogen catalytic region of human MASP-2

Structural highlights

1zjk is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	MASP2 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[MASP2_HUMAN] Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:613791]. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.^[1] ^[2]

Function

[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.^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[4]

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

References

↑ Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, Sjoholm AG, Fugger L, Jensenius JC. Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med. 2003 Aug 7;349(6):554-60. PMID:12904520 doi:http://dx.doi.org/10.1056/NEJMoa022836
↑ Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, Eiberg H, Gadjeva M, Ruseva M, Jensenius JC. Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 2007 Mar;8(2):154-63. Epub 2007 Jan 25. PMID:17252003 doi:10.1038/sj.gene.6364373
↑ Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol. 2000 Sep 1;165(5):2637-42. PMID:10946292
↑ Gal P, Harmat V, Kocsis A, Bian T, Barna L, Ambrus G, Vegh B, Balczer J, Sim RB, Naray-Szabo G, Zavodszky P. A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations. J Biol Chem. 2005 Sep 30;280(39):33435-44. Epub 2005 Jul 21. PMID:16040602 doi:10.1074/jbc.M506051200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zjk"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1zjk]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZJK FirstGlance]. <br>
-</td></tr><tr><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])</td></tr>
+</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])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zjk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1zjk RCSB], [http://www.ebi.ac.uk/pdbsum/1zjk 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=1zjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zjk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1zjk RCSB], [http://www.ebi.ac.uk/pdbsum/1zjk PDBsum]</span></td></tr>
-<table>
+</table>
 == 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>
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ambrus, G.]]
+[[Category: Ambrus, G]]
-[[Category: Balczer, J.]]
+[[Category: Balczer, J]]
-[[Category: Barna, L.]]
+[[Category: Barna, L]]
-[[Category: Bian, T.]]
+[[Category: Bian, T]]
-[[Category: Gal, P.]]
+[[Category: Gal, P]]
-[[Category: Harmat, V.]]
+[[Category: Harmat, V]]
-[[Category: Kocsis, A.]]
+[[Category: Kocsis, A]]
-[[Category: Naray-Szabo, G.]]
+[[Category: Naray-Szabo, G]]
-[[Category: Sim, R B.]]
+[[Category: Sim, R B]]
-[[Category: Vegh, B.]]
+[[Category: Vegh, B]]
-[[Category: Zavodszky, P.]]
+[[Category: Zavodszky, P]]
 [[Category: Beta barrel]]
 [[Category: Hydrolase]]
 [[Category: Modular protein]]

1zjk

From Proteopedia

Revision as of 10:09, 8 January 2015

Crystal structure of the zymogen catalytic region of human MASP-2

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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