1zjk
From Proteopedia
(New page: 200px<br /> <applet load="1zjk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zjk, resolution 2.18Å" /> '''Crystal structure o...) |
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| - | [[Image:1zjk.gif|left|200px]]<br /> | + | [[Image:1zjk.gif|left|200px]]<br /><applet load="1zjk" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zjk" size=" | + | |
caption="1zjk, resolution 2.18Å" /> | caption="1zjk, resolution 2.18Å" /> | ||
'''Crystal structure of the zymogen catalytic region of human MASP-2'''<br /> | '''Crystal structure of the zymogen catalytic region of human MASP-2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Few reports have described in detail a true autoactivation process, where | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZJK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1ZJK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of 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]. |
==Reference== | ==Reference== | ||
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[[Category: Kocsis, A.]] | [[Category: Kocsis, A.]] | ||
[[Category: Naray-Szabo, G.]] | [[Category: Naray-Szabo, G.]] | ||
| - | [[Category: Sim, R | + | [[Category: Sim, R B.]] |
[[Category: Vegh, B.]] | [[Category: Vegh, B.]] | ||
[[Category: Zavodszky, P.]] | [[Category: Zavodszky, P.]] | ||
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[[Category: modular protein]] | [[Category: modular protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:16:17 2008'' |
Revision as of 14:16, 21 February 2008
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Crystal structure of the zymogen catalytic region of human MASP-2
Contents |
Overview
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.
Disease
Known disease associated with this structure: MASP2 deficiency OMIM:[605102]
About this Structure
1ZJK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:16:17 2008
Categories: Homo sapiens | Single protein | Ambrus, G. | Balczer, J. | Barna, L. | Bian, T. | Gal, P. | Harmat, V. | Kocsis, A. | Naray-Szabo, G. | Sim, R B. | Vegh, B. | Zavodszky, P. | Beta barrel | Modular protein
