3tvj

Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold

spinqualitylabelsall models 3tvj, resolution 1.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tvj is a 3 chain structure with sequence from Desert locust and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 4djz Gene: MASP2 (HUMAN), GenBank: Y09605.1 (Desert locust) Activity: Mannan-binding lectin-associated serine protease-2, with EC number 3.4.21.104 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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. [SGP1_SCHGR] In vitro, SGPI-1/SGCI is active against alpha-chymotrypsin and trypsin while SGPI-2/SGTI is active against alpha-chymotrypsin and pancreatic elastase. Publication Abstract from PubMed The lectin pathway is an antibody-independent activation route of the complement system. It provides immediate defense against pathogens and altered self-cells, but it also causes severe tissue damage after stroke, heart attack and other ischemia reperfusion injuries. The pathway is triggered by target-binding of pattern recognition molecules leading to the activation of zymogen mannan-binding lectin-associated serine proteases (MASPs). MASP-2 is considered as the autonomous pathway-activator while MASP-1 as an auxiliary component. We evolved a pair of monospecific MASP inhibitors. In accordance with the key role of MASP-2, the MASP-2 inhibitor completely blocks the lectin pathway activation. Importantly, the MASP-1 inhibitor does the same demonstrating that MASP-1 is not an auxiliary but an essential pathway component. We report the first Michaelis-like complex structures of MASP-1 and MASP-2 formed with substrate-like inhibitors. The 1.28 A resolution MASP-2 structure reveals significant plasticity of the protease suggesting that either an induced fit or a conformational selection mechanism should contribute to the extreme specificity of the enzyme. Monospecific inhibitors show that both mannan-binding lectin-associated serine protease (MASP)-1 and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2.,Heja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G J Biol Chem. 2012 Apr 16. PMID:22511776 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mannan-binding lectin serine protease

Proteopedia Page Contributors and Editors (what is this?)

OCA