1zjk

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spinqualitylabelsall models 1zjk, resolution 2.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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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