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

BRENDA support

Literature summary for 3.4.21.61 extracted from

  • Ni, Y.G.; Condra, J.H.; Orsatti, L.; Shen, X.; Di Marco, S.; Pandit, S.; Bottomley, M.J.; Ruggeri, L.; Cummings, R.T.; Cubbon, R.M.; Santoro, J.C.; Ehrhardt, A.; Lewis, D.; Fisher, T.S.; Ha, S.; Njimoluh, L.; Wood, D.D.; Hammond, H.A.; Wisniewski, D.; Volpari, C.; Noto, A.; Lo Surdo, P.; Hubbard, B.; Carfi, A.
    A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake (2010), J. Biol. Chem., 285, 12882-12891.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.21.61

Application

Application Comment Organism
additional information 1G08 fragment antigen binding represents a useful new tool for delineating the mechanism of PCSK9 uptake and low density lipoprotein receptor degradation Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
full-length and mutant PCSK9-V5-His proteins expressed in HEK-293 cells. Truncated PCSK9DELTAC (Gln-31-Ala-451) proteins with a C-terminal His tag expressed in Escherichia coli BL21 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
E607A/K609A/E612N mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding Homo sapiens
additional information 1G08 fragment antigen binding fails to bind a truncated form of PCSK9 lacking the C-terminal domain. Lack of the C-terminal domain compromises the ability of PCSK9 to internalize into cells, and to inhibit low density lipoprotein uptake Homo sapiens
R549A mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding Homo sapiens
R580A/R582A mutation does not affect the overall integrity of the PCSK9 protein, shows similar cellular uptake potencies as the wild-type, impairs 1G08-PCSK9 binding Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information in HEK-293 and Hep-G2 cells, 1G08 fragment antigen binding reduces 50% the PCSK9-dependent inhibitory effects on low density lipoprotein uptake. 1G08 fragment antigen binding does not affect the PCSK9-low density lipoprotein receptor interaction but inhibits the internalization of PCSK9 in these cells. 1G08 fragment antigen binding binds a region of beta-strands encompassing Arg-549, Arg-580, Arg-582, Glu-607, Lys-609, and Glu-612 in the PCSK9 C-terminal domain. The membrane associated protein Annexin A2 does not affect 1G08-PCSK9 binding Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
75979
-
 1 * 75979, purified PCSK9, gel filtration. 1* 45708, purified PCSK9DELTAC, gel filtration Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q8NBP7
-
-

Purification (Commentary)

Purification (Comment) Organism
gel filtration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
low density lipoprotein receptor
-
 Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
monomer 1 * 75979, purified PCSK9, gel filtration. 1* 45708, purified PCSK9DELTAC, gel filtration Homo sapiens

Synonyms

Synonyms Comment Organism
PCSK9
-
 Homo sapiens
proprotein convertase subtilisin-like/kexin type 9
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
additional information
-
 at 20°C in 0.05 ml of buffer containing 10 mM Hepes, pH 7.4, 150 mM NaCl, 0.1 mM CaCl2, and 0.05% (w/v) bovine serum albumin: 0.0000048 mM with 1G08 fragment antigen binding, when wild-type expressed in HEK-293 cells, 0.0000150 mM with 1G08 fragment antigen binding, when wild-type expressed in Hep-G2 cells, 0.001 mM with 1G08 fragment antigen binding, when mutant R549A , mutant R580A/R582A and mutant E607A/K609A/E612N expressed in HEK-293 cells Homo sapiens additional information

General Information

General Information Comment Organism
physiological function PCSK9 binds to the low density lipoprotein receptor and leads to low density lipoprotein receptor degradation and inhibition of plasma low density lipoprotein cholesterol clearance. PCSK9 C-terminal domain contributes to its inhibition of low density lipoprotein receptor function mainly through its role in the cellular uptake of PCSK9 and low-density lipoprotein receptor complex Homo sapiens