[NMR paper] 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.
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.
Related ArticlesGentamicin 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.
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.
NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin ?(1) ?(1).
NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin ?(1) ?(1).
NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin ?(1) ?(1).
Proteins. 2011 May 10;
Authors: Carbajo RJ, Sanz L, Mosulén S, Pérez A, Marcinkiewicz C, Pineda-Lucena A, Calvete JJ
NMR analysis of four recombinant jerdostatin molecules was assessed to define the structural basis of two naturally occurring gain-of-function events: C-terminal dipeptide processing and...
[NMR paper] Binding of sucrose octasulphate to the C-type lectin-like domain of the recombinant n
Binding of sucrose octasulphate to the C-type lectin-like domain of the recombinant natural killer cell receptor NKR-P1A observed by NMR spectroscopy.
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Chembiochem. 2002 Nov 4;3(11):1072-7
Authors: Kogelberg H, Frenkiel TA, Birdsall B, Chai W, Muskett FW
NKR-P1A is a C-type lectin-like receptor on natural killer cells believed to be involved in the cytotoxicity of these cells....
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[NMR paper] NMR solution structure of complement-like repeat CR3 from the low density lipoprotein
NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin.
Related Articles NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin.
J Biol Chem. 2000 Feb 4;275(5):3264-9
Authors: Dolmer K, Huang W, Gettins PG
We have used NMR methods to determine the...
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[NMR paper] NMR analysis reveals a positively charged hydrophobic domain as a common motif to bou
NMR analysis reveals a positively charged hydrophobic domain as a common motif to bound acetylcholine and d-tubocurarine.
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Biochemistry. 1994 Jan 25;33(3):644-50
Authors: Fraenkel Y, Gershoni JM, Navon G
A complete 1H assignment of d-tubocurarine was carried out using 1D and 2D NMR techniques. Geometries of free acetylcholine (ACh) and d-tubocurarine were compared with those of the ligands bound to a...
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[NMR paper] Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase fro
Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase from Escherichia coli studied by 1H NMR. Different properties of the large protein subunit and the holoenzyme.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_FREE_120x27.gif Related Articles Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase from Escherichia coli studied by 1H NMR. Different properties of the large protein subunit and the holoenzyme.
Eur J Biochem. 1992 Sep...
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[NMR paper] Secondary structure of a complement control protein module by two-dimensional 1H NMR.
Secondary structure of a complement control protein module by two-dimensional 1H NMR.
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Biochemistry. 1991 Jan 29;30(4):997-1004
Authors: Barlow PN, Baron M, Norman DG, Day AJ, Willis AC, Sim RB, Campbell ID
The complement control protein (CCP) module (also known as the short consensus repeat) is a consensus sequence of about 60 amino acid residues which is thought to fold independently. It occurs over 140 times in more than 20 extracellular...
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[NMR paper] NMR solution structure of complement-like repeat CR8 from the low density lipoprotein
NMR solution structure of complement-like repeat CR8 from the low density lipoprotein receptor-related protein.
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J Biol Chem. 1999 May 14;274(20):14130-6
Authors: Huang W, Dolmer K, Gettins PG
The low density lipoprotein receptor-related protein is a member of the low density...
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.
Linear Mode
