Literature summary for 3.4.21.B7 extracted from

Heja, D.; Harmat, V.; Fodor, K.; Wilmanns, M.; Dobo, J.; Kekesi, K.A.; Zavodszky, P.; Gal, P.; Pal, G.
Monospecific inhibitors show that both mannan-binding lectin-associated serine protease-1 (MASP-1) and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2 (2012), J. Biol. Chem., 287, 20290-20300.

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Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of the CCP1-CCP2-SP fragment of enzyme MASP-1 in Escherichia coli	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
in complex with Schistocerca gregaria protease inhibitor-2 variant VCTKLWCN, to 1.28 A resolution. Structure reveals significant plasticity of the protease	Homo sapiens
MASP-1 catalytic domain in complex with protease inhibitor SGPI-1, recombinant CCP1-CCP2-SP fragment of MASP-1 and SGMI-1 inhibitor are mixed in a 2:3 molar ratio and concentrated to 5 mg/ml, hanging drop vapor diffusion method, mixing of 0.001 ml of protein and 0.001 ml of reservoir solution comprising 0.1 M HEPES, pH 7.0, 25% PEG 1000, 0.3 M NaNO3, at 20°C, crystal structure determination and analysis at 3.2 A resolution, molecular replacement	Homo sapiens

Crystallization (Comment)

Organism

in complex with Schistocerca gregaria protease inhibitor-2 variant VCTKLWCN, to 1.28 A resolution. Structure reveals significant plasticity of the protease

Homo sapiens

MASP-1 catalytic domain in complex with protease inhibitor SGPI-1, recombinant CCP1-CCP2-SP fragment of MASP-1 and SGMI-1 inhibitor are mixed in a 2:3 molar ratio and concentrated to 5 mg/ml, hanging drop vapor diffusion method, mixing of 0.001 ml of protein and 0.001 ml of reservoir solution comprising 0.1 M HEPES, pH 7.0, 25% PEG 1000, 0.3 M NaNO3, at 20°C, crystal structure determination and analysis at 3.2 A resolution, molecular replacement

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
ACTRKLCW	a Schistocerca gregaria protease inhibitor-1 P4-P4' sequence mutant	Homo sapiens
MCTRKLCW	a Schistocerca gregaria protease inhibitor-1 P4-P4' sequence mutant	Homo sapiens
MCTRKLCY	a Schistocerca gregaria protease inhibitor-1 P4-P4' sequence mutant	Homo sapiens
additional information	no inhibition by Schistocerca gregaria protease inhibitor-2, SGMI-2, and sunflower MASP inhibitor-2, SFMI-2, but slight inhibition by inhibitor mutants, overview; Schistocerca gregaria protease inhibitor-2 variant VCTKLWCN is specific for isoform MASP-2 and not inhibitory for isoform MASP-1	Homo sapiens
Schistocerca gregaria protease inhibitor-1	SGMI-1, sequence P4-P4' is FCTRKLCY, the structure of the MASP-1-SGMI-1 complex does not support the induced fit or conformational selection substrate-binding model, structure analysis, detailed overview	Homo sapiens
Schistocerca gregaria protease inhibitor-2 variant FCTRKLCY	randomization of positions P4, P2, P1, P1', P2', and P4' of the protease binding loop while keeping the structurally indispensable Cys at P3 and P3' leads to monospecific MASP inhibitors. Inhibitor variant FCTRKLCY is specific for isoform MASP-1, treatment completely blocks the lectin pathway activation, demonstrating that MASP-1 is not an auxiliary but an essential pathway component	Homo sapiens
sunflower MASP inhibitor-1	SFMI-1, sequence P4-P4' is ICSRSLPP	Homo sapiens
VCTRLWCE	a sunflower MASP inhibitor-2 P4-P4' sequence mutant, only slight inhibition	Homo sapiens
VCTRLWCN	a sunflower MASP inhibitor-2 P4-P4' sequence mutant, only slight inhibition	Homo sapiens
VCTRLYCN	a sunflower MASP inhibitor-2 P4-P4' sequence mutant, only slight inhibition	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P48740	-	-

Synonyms

Synonyms	Comment	Organism
MASP-1	-	Homo sapiens

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.000007	-	Schistocerca gregaria protease inhibitor-2 variant FCTRKLCY	pH not specified in the publication, temperature not specified in the publication	Homo sapiens
0.000007	-	Schistocerca gregaria protease inhibitor-1	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.000014	-	MCTRKLCY	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.00002	-	MCTRKLCW	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.000027	-	ACTRKLCW	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.000065	-	sunflower MASP inhibitor-1	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.087	-	VCTRLWCN	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.153	-	VCTRLWCE	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens
0.176	-	VCTRLYCN	pH and temperature not specified in the publication, recombinant enzyme	Homo sapiens

General Information

General Information	Comment	Organism
metabolism	target binding of pattern recognition molecules leads to the activation of zymogen mannan-binding lectin-associated serine proteases and triggers the lectin pathway, an antibody-independent activation route of the complement system, which provides immediate defense against pathogens and altered self-cells, but also causes severe tissue damage after stroke, heart attack, and other ischemia reperfusion injuries. MASP-2 and MASP-1 are both essential pathway components	Homo sapiens