PDBsum entry 2m0p

Lipid binding protein

PDB id: 2m0p

Contents

Protein chain

46 a.a.

Metals

_CA

PDB id:

2m0p

Name:

Lipid binding protein

Title:

Solution structure of the tenth complement type repeat of human megalin

Structure:

Low-density lipoprotein receptor-related protein 2. Chain: a. Synonym: lrp-2, glycoprotein 330, gp330, megalin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lrp2. Expressed in: komagataella pastoris. Expression_system_taxid: 4922.

NMR struc:

20 models

Authors:

R.Dagil,B.Kragelund

Key ref:

R.Dagil et al. (2013). Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats: insight from the nmr structure of the 10th complement type repeat domain alone and in complex with gentamicin. J Biol Chem, 288, 4424-4435. PubMed id: 23275343

Date:

01-Nov-12 Release date: 09-Jan-13

Protein chain

P98164  (LRP2_HUMAN) -  Low-density lipoprotein receptor-related protein 2 from Homo sapiens

Seq: 4655 a.a.

Struc: 46 a.a.

J Biol Chem 288:4424-4435 (2013)

PubMed id: 23275343

Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats: insight from the nmr structure of the 10th complement type repeat domain alone and in complex with gentamicin.

R.Dagil, C.O'Shea, A.Nykjær, A.M.Bonvin, B.B.Kragelund.

ABSTRACT

Gentamicin is an aminoglycoside widely used in treatments of, in particular, enterococcal, mycobacterial, and severe Gram-negative bacterial infections. Large doses of gentamicin cause nephrotoxicity and ototoxicity, entering the cell via the receptor megalin. Until now, no structural information has been available to describe the interaction with gentamicin in atomic detail, and neither have any three-dimensional structures of domains from the human megalin receptor been solved. To address this gap in our knowledge, we have solved the NMR structure of the 10th complement type repeat of human megalin and investigated its interaction with gentamicin. Using NMR titration data in HADDOCK, we have generated a three-dimensional model describing the complex between megalin and gentamicin. Gentamicin binds to megalin with low affinity and exploits the common ligand binding motif previously described (Jensen, G. A., Andersen, O. M., Bonvin, A. M., Bjerrum-Bohr, I., Etzerodt, M., Thogersen, H. C., O'Shea, C., Poulsen, F. M., and Kragelund, B. B. (2006) J. Mol. Biol. 362, 700-716) utilizing the indole side chain of Trp-1126 and the negatively charged residues Asp-1129, Asp-1131, and Asp-1133. Binding to megalin is highly similar to gentamicin binding to calreticulin. We discuss the impact of this novel insight for the future structure-based design of gentamicin antagonists.