Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary 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.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.4.21.46 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
3.4.21.46 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)

EC Number Crystallization (Comment) Organism
3.4.21.46 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
3.4.21.46 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

EC Number Inhibitors Comment Organism Structure
3.4.21.46 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
3.4.21.46 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)

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

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.46 Homo sapiens P00746
-
-
3.4.21.46 Macaca fascicularis
-
-
-

Purification (Commentary)

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

Substrates and Products (Substrate)

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

Synonyms

EC Number Synonyms Comment Organism
3.4.21.46 factor D
-
Macaca fascicularis
3.4.21.46 factor D
-
Homo sapiens

General Information

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