2MG9

Truncated EGF-A

Summary for 2MG9

• Entry DOI: 10.2210/pdb2mg9/pdb
• NMR Information: BMRB: 19593
• Descriptor: Low-density lipoprotein receptor, CALCIUM ION (2 entities in total)
• Functional Keywords: egf-a, disulfide rich, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01130
• Total number of polymer chains: 1
• Total formula weight: 2812.14

Authors

Schroeder, C.I.,Rosengren, K. (deposition date: 2013-10-30, release date: 2014-04-02, Last modification date: 2024-11-06)

Primary citation

Schroeder, C.I.,Swedberg, J.E.,Withka, J.M.,Rosengren, K.J.,Akcan, M.,Clayton, D.J.,Daly, N.L.,Cheneval, O.,Borzilleri, K.A.,Griffor, M.,Stock, I.,Colless, B.,Walsh, P.,Sunderland, P.,Reyes, A.,Dullea, R.,Ammirati, M.,Liu, S.,McClure, K.F.,Tu, M.,Bhattacharya, S.K.,Liras, S.,Price, D.A.,Craik, D.J.
Design and Synthesis of Truncated EGF-A Peptides that Restore LDL-R Recycling in the Presence of PCSK9 In Vitro.
Chem.Biol., 21:284-294, 2014

PubMed Abstract: Disrupting the binding interaction between proprotein convertase (PCSK9) and the epidermal growth factor-like domain A (EGF-A domain) in the low-density lipoprotein receptor (LDL-R) is a promising strategy to promote LDL-R recycling and thereby lower circulating cholesterol levels. In this study, truncated 26 amino acid EGF-A analogs were designed and synthesized, and their structures were analyzed in solution and in complex with PCSK9. The most potent peptide had an increased binding affinity for PCSK9 (KD = 0.6 μM) compared with wild-type EGF-A (KD = 1.2 μM), and the ability to increase LDL-R recycling in the presence of PCSK9 in a cell-based assay.

PubMed: 24440079
DOI: 10.1016/j.chembiol.2013.11.014

Experimental method

SOLUTION NMR