Literature summary for 3.4.21.46 extracted from

Katschke, K.J.; Wu, P.; Ganesan, R.; Kelley, R.F.; Mathieu, M.A.; Hass, P.E.; Murray, J.; Kirchhofer, D.; Wiesmann, C.; van Lookeren Campagne, M.
Inhibiting alternative pathway complement activation by targeting the factor D exosite (2012), J. Biol. Chem., 287, 12886-12892.

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Application

Application	Comment	Organism
drug development	the enzyme's exosite is a target for design of specific inhibitors for inhibition of the pathway complement activation in advanced dry age-related macular degeneration	Macaca fascicularis
drug development	the enzyme's exosite is a target for design of specific inhibitors for inhibition of the pathway complement activation in advanced dry age-related macular degeneration	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme in complex with anti-factor D Fab fragment, sitting drop vapor diffusion method, 20 mg/ml protein in 20 mM HEPES, pH 7.2, and 200 mM NaCl, is mixed with an equal volume of crystallization buffer containing 0.1 M MES, pH 6.5, 25% PEG monomethyl ether 550, 0.01 M zinc sulfate, and 3% 6-aminohexanoic acid, 1 day, 19°C, X-ray diffraction structure determination and analysis at 2.3 A resolution	Macaca fascicularis
purified enzyme in complex with anti-factor D Fab fragment, sitting drop vapor diffusion method, 30 mg/ml protein in 20 mM HEPES, pH 7.2, and 200 mM NaCl, is mixed with an equal volume of crystallization buffer containing 0.1 M Tris-HCl, pH 8.5, 0.2 M ammonium phosphate, 50% 2-methyl-2,4-pentanediol, and 0.01 M hexamine cobalt(III) chloride, 6 days, 4°C, X-ray diffraction structure determination and analysis at 2.4 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified enzyme in complex with anti-factor D Fab fragment, sitting drop vapor diffusion method, 20 mg/ml protein in 20 mM HEPES, pH 7.2, and 200 mM NaCl, is mixed with an equal volume of crystallization buffer containing 0.1 M MES, pH 6.5, 25% PEG monomethyl ether 550, 0.01 M zinc sulfate, and 3% 6-aminohexanoic acid, 1 day, 19°C, X-ray diffraction structure determination and analysis at 2.3 A resolution

Macaca fascicularis

purified enzyme in complex with anti-factor D Fab fragment, sitting drop vapor diffusion method, 30 mg/ml protein in 20 mM HEPES, pH 7.2, and 200 mM NaCl, is mixed with an equal volume of crystallization buffer containing 0.1 M Tris-HCl, pH 8.5, 0.2 M ammonium phosphate, 50% 2-methyl-2,4-pentanediol, and 0.01 M hexamine cobalt(III) chloride, 6 days, 4°C, X-ray diffraction structure determination and analysis at 2.4 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
anti-factor D Fab fragment	an Escherichia coli-expressed, humanized Fab fragment, derived from monoclonal antibody 166-32, and designed as specific enzyme inhibitor targeting the exosite. Anti-factor D Fab fragment prevents factor D-mediated proteolytic activation of its macromolecular substrate C3bB, but not proteolysis of a small synthetic substrate, indicating that the inhibitor does not block access of the substrate to the catalytic site, binding structure and inhibitory mechanism, overview. The structures show that the AFD-binding site includes surface loops of the enzyme that form part of the enzyme's exosite. Anti-factor D Fab fragment inhibits the enzyme proteolytic function by interfering with macromolecular substrate access rather than by inhibiting the enzyme catalysis	Homo sapiens
anti-factor D Fab fragment	an Escherichia coli-expressed, humanized Fab fragment, derived from monoclonal antibody 166-32, and designed as specific enzyme inhibitor targeting the exosite. Anti-factor D Fab fragment prevents factor D-mediated proteolytic activation of its macromolecular substrate C3bB, but not proteolysis of a small synthetic substrate, indicating that the inhibitor does not block access of the substrate to the catalytic site, binding structure and inhibitory mechanism, overview. The structures show that the AFD-binding site includes surface loops of the enzyme that form part of the enzyme's exosite. Anti-factor D Fab fragment inhibits the enzyme proteolytic function by interfering with macromolecular substrate access rather than by inhibiting the enzyme catalysis	Macaca fascicularis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
complement component C3bB + H2O	Macaca fascicularis	-	?	-	?
complement component C3bB + H2O	Homo sapiens	-	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P00746	-	-
Macaca fascicularis	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
enzyme and inhibitor by gel filtration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
complement component C3bB + H2O	-	Macaca fascicularis	?	-	?
complement component C3bB + H2O	-	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
factor D	-	Macaca fascicularis
factor D	-	Homo sapiens

General Information

General Information	Comment	Organism
physiological function	targeting of the enzyme's exosite causes inhibition of the pathway complement activation	Macaca fascicularis
physiological function	targeting of the enzyme's exosite causes inhibition of the pathway complement activation	Homo sapiens