6XIB
PCSK9(deltaCRD) in complex with cyclic peptide 30
Summary for 6XIB
| Entry DOI | 10.2210/pdb6xib/pdb |
| Descriptor | Proprotein convertase subtilisin/kexin type 9, Peptide 30, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | protein-peptide complex, cyclic peptide, non-natural amino acids, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 48242.18 |
| Authors | Orth, P. (deposition date: 2020-06-19, release date: 2020-11-18, Last modification date: 2024-04-24) |
| Primary citation | Alleyne, C.,Amin, R.P.,Bhatt, B.,Bianchi, E.,Blain, J.C.,Boyer, N.,Branca, D.,Embrey, M.W.,Ha, S.N.,Jette, K.,Johns, D.G.,Kerekes, A.D.,Koeplinger, K.A.,LaPlaca, D.,Li, N.,Murphy, B.,Orth, P.,Ricardo, A.,Salowe, S.,Seyb, K.,Shahripour, A.,Stringer, J.R.,Sun, Y.,Tracy, R.,Wu, C.,Xiong, Y.,Youm, H.,Zokian, H.J.,Tucker, T.J. Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design. J.Med.Chem., 63:13796-13824, 2020 Cited by PubMed Abstract: Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a key regulator of plasma LDL-cholesterol (LDL-C) and a clinically validated target for the treatment of hypercholesterolemia and coronary artery disease. In this paper, we describe a series of novel cyclic peptides derived from an mRNA display screen which inhibit the protein-protein interaction between PCSK9 and LDLR. Using a structure-based drug design approach, we were able to modify our original screening lead to optimize the potency and metabolic stability and minimize the molecular weight to provide novel bicyclic next-generation PCSK9 inhibitor peptides such as . These next-generation peptides serve as a critical foundation for continued exploration of potential oral, once-a-day PCSK9 therapeutics for the treatment of cardiovascular disease. PubMed: 33170686DOI: 10.1021/acs.jmedchem.0c01084 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.546 Å) |
Structure validation
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