Calcium-Independent Inhibition of PCSK9 by Affinity-Improved Variants of the LDL Receptor EGF(A) Domain

LDL (low‐density lipoprotein) receptor (LDLR) binds to its negative regulator proprotein convertase subtilisin/kexin type 9 (PCSK9) through the first EGF (epidermal growth factor‐like) domain [EGF(A)]. The isolated EGF(A) domain is a poor antagonist due to its low affinity for PCSK9. To improve bind...

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Veröffentlicht in:	Journal of molecular biology 2012-10, Vol.422 (5), p.685-696
Hauptverfasser:	Zhang, Yingnan, Zhou, Lijuan, Kong-Beltran, Monica, Li, Wei, Moran, Paul, Wang, Jianyong, Quan, Clifford, Tom, Jeffrey, Kolumam, Ganesh, Elliott, J. Michael, Skelton, Nicholas J., Peterson, Andrew S., Kirchhofer, Daniel
Format:	Artikel
Sprache:	eng
Schlagworte:	amines Amino Acid Sequence Amino Acid Substitution bacteriophages binding capacity calcium Calcium - metabolism clones Competition Enzyme-linked immunosorbent assay Epidermal growth factor epidermal growth factor receptors Fusion protein Kexin Lipoprotein (low density) receptors lipoprotein receptors Lipoproteins (low density) low density lipoprotein Models, Molecular Molecular Sequence Data Mutant Proteins - genetics Mutant Proteins - metabolism Mutation Mutation, Missense PCSK9 inhibition by EGF(A) domain variants Peptide Library Phage display Proprotein Convertase 9 Proprotein Convertases - antagonists & inhibitors Protein Binding Protein Interaction Domains and Motifs Receptors, LDL - genetics Receptors, LDL - metabolism Serine Endopeptidases Subtilisin
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