1ZJK

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

Summary for 1ZJK

• Entry DOI: 10.2210/pdb1zjk/pdb
• Descriptor: Mannan-binding lectin serine protease 2 (2 entities in total)
• Functional Keywords: beta barrel, modular protein, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: O00187
• Total number of polymer chains: 1
• Total formula weight: 44031.71

Authors

Gal, P.,Harmat, V.,Kocsis, A.,Bian, T.,Barna, L.,Ambrus, G.,Vegh, B.,Balczer, J.,Sim, R.B.,Naray-Szabo, G.,Zavodszky, P. (deposition date: 2005-04-29, release date: 2005-07-26, Last modification date: 2024-10-30)

Primary citation

Gal, P.,Harmat, V.,Kocsis, A.,Bian, T.,Barna, L.,Ambrus, G.,Vegh, B.,Balczer, J.,Sim, R.B.,Naray-Szabo, G.,Zavodszky, P.
A True Autoactivating Enzyme: Structural insight into mannose-binding lectin-associated serine protease-2 activations
J.Biol.Chem., 280:33435-33444, 2005

PubMed Abstract: 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.

PubMed: 16040602
DOI: 10.1074/jbc.M506051200

Experimental method

X-RAY DIFFRACTION (2.18 Å)