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spinqualitylabelsall models PDB ID 1zjk Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.18Å
Gene:	MASP2 (Homo sapiens)
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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

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