Ligand binding site of tear lipocalin: contribution of a trigonal cluster of charged residues probed by 8-anilino-1-naphthalenesulfonic acid

Biochemistry
O K GasymovB J Glasgow

Abstract

Human tear lipocalin (TL) exhibits diverse functions, most of which are linked to ligand binding. To map the binding site of TL for some amphiphilic ligands, we capitalized on the hydrophobic and hydrophilic properties of 8-anilino-1-naphthalenesulfonic acid (ANS). In single Trp mutants, resonance energy transfer from Trp to ANS indicates that the naphthalene group of ANS is proximate to Leu105 in the cavity. Binding energies of TL to ANS and its analogues reveal contributions from electrostatic interactions. The sulfonate group of ANS interacts strongly with the nonconserved intracavitary residue Lys114 and less with neighboring residues His84 and Glu34. This trigonal cluster of residues may play a role in the ligand recognition site for some negatively charged ligands. Because many drugs possess sulfonate groups, the trigonal cluster-sulfonate interaction can also be exploited as a lipocalin-based drug delivery mechanism. The binding of lauric acid and its analogues shows that fatty acids assume heterogeneous orientations in the cavity of TL. Predominantly, the hydrocarbon tail is buried in the cavity of TL and the carboxyl group is oriented toward the mouth. However, TL can also interact, albeit relatively weakly, with fatty...Continue Reading

References

May 17, 1976·European Journal of Biochemistry·U CoganM Shinitzky
Oct 1, 1985·Journal of Clinical Chemistry and Clinical Biochemistry. Zeitschrift Für Klinische Chemie Und Klinische Biochemie·D BozimowskiB Zak
Jan 1, 1974·CRC Critical Reviews in Biochemistry·E H Strickland
Mar 1, 1982·Experimental Eye Research·M E Selsted, R J Martinez
May 1, 1995·Current Eye Research·B J GlasgowW L Hubbell
Nov 1, 1993·Current Eye Research·B J GlasgowJ B Bateman
Aug 1, 1995·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·B J Glasgow
Aug 15, 1996·The Biochemical Journal·D R Flower
Jan 17, 1997·The Journal of Biological Chemistry·W van't HofA V Amerongen
Nov 5, 1997·Biochemical and Biophysical Research Communications·O K GasymovB J Glasgow
Jul 24, 1998·Biochimica Et Biophysica Acta·O K GasymovB J Glasgow
Nov 5, 1999·Journal of Molecular Biology·S Kumar, R Nussinov
Mar 15, 2000·Protein Science : a Publication of the Protein Society·O K GasymovB J Glasgow
Apr 19, 2000·The Biochemical Journal·T N YusifovB J Glasgow
Nov 4, 2000·Biochimica Et Biophysica Acta·B Redl
Nov 4, 2000·Biochimica Et Biophysica Acta·A Skerra
Feb 19, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Petra WojnarBernhard Redl
Jul 24, 2003·Protein Science : a Publication of the Protein Society·Maddalena ColliniGiancarlo Baldini
Apr 27, 2004·Experimental Eye Research·A J BronL W Voon
Apr 27, 2004·Experimental Eye Research·James P McCulley, Ward E Shine
Jul 12, 2005·Colloids and Surfaces. B, Biointerfaces·F MianoV Enea
Sep 28, 2005·Investigative Ophthalmology & Visual Science·Oktay K GasymovBen J Glasgow
Oct 21, 2005·Biochimica Et Biophysica Acta·Scott M Gouveia, John M Tiffany
Apr 15, 2006·The Oncologist·David S Goodsell
Feb 27, 2007·Biochimica Et Biophysica Acta·Oktay K Gasymov, Ben J Glasgow
Jul 24, 2007·Current Opinion in Biotechnology·Arne Skerra
Oct 20, 2007·Archives of Biochemistry and Biophysics·Oktay K GasymovBen J Glasgow
Nov 22, 2007·Photochemistry and Photobiology·Oktay K GasymovBen J Glasgow

❮ Previous
Next ❯

Citations

Jun 19, 2013·Experimental Eye Research·Igor A Butovich
Mar 24, 2012·Biochemistry·Oktay K GasymovBen J Glasgow
Jul 29, 2009·The Ocular Surface·Jadwiga C WojtowiczJames P McCulley
Sep 30, 2010·Journal of Photochemistry and Photobiology. B, Biology·Jishnu ChakrabortyUmesh Chandra Halder
Feb 18, 2014·Biochimica Et Biophysica Acta·Tamara StaudingerBen J Glasgow
Dec 5, 2009·Current Eye Research·Jean M CrowSusann G Remington
Mar 9, 2020·Journal of Fluorescence·Valentín De la Cruz-TorresJosé G Sampedro

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.