May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Intracavitary Lys114 of Tear Lipocalin Permits Opposing Orientations of Fatty Acids: Potential Mechanism for Stabilization of the Surface Film of Tears
Author Affiliations & Notes
  • B. J. Glasgow
    JSEI/UCLA, Los Angeles, California
    Pathology & Ophthalmology,
  • A. R. Abduragimov
    JSEI/UCLA, Los Angeles, California
  • O. K. Gasymov
    JSEI/UCLA, Los Angeles, California
  • Footnotes
    Commercial Relationships  B.J. Glasgow, None; A.R. Abduragimov, None; O.K. Gasymov, None.
  • Footnotes
    Support  NIH Grant EY11224
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5289. doi:
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      B. J. Glasgow, A. R. Abduragimov, O. K. Gasymov; Intracavitary Lys114 of Tear Lipocalin Permits Opposing Orientations of Fatty Acids: Potential Mechanism for Stabilization of the Surface Film of Tears. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5289.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Previous work suggests that a trigonal cluster of charged residues in tear lipocalin (TL) may play a role in ligand recognition of negatively charged ligands. A docking study was performed to test the plausibility of an interaction between the sulfonate group of ANS and side chains of K114, H84 and E34 of TL. A comparison is made to the related lipocalin, β lactoglobulin (BLG).

Methods: : ANS was docked into the TL cavity using ArgusLab 4.0.1 software (Planaria Software LLC). X-ray coordinates were input for the crystal structure of TL (PDB: 1XKI). Parameters for ANS were taken from the ANS-MurA (UDPGlcNAc enolpyruvyltransferase (EC )) complex (PDB: 1EVN). The "high precision" mode was employed and results were visualized with DeepView/ Swiss-PdbViewer v.3.7 (GlaxoSmithKline R&D). Binding energies were calculated and analyzed for several possible docking solutions.

Results: : Multiple solutions were generated for the ANS-TL complex with energy values ranging from -11.9 to -10.5 kcal/mol. In accord with multiple solutions, the decay associated spectrum (for 17 ns) of ANS-TL complex has been shown to be heterogeneous and could not be fit to a single log-normal component. In comparison, BLG shows much lower interaction energy with ANS, -6.2 kcal/mol. Despite 23% sequence identity and superimposable calyxes, the binding affinity to ANS for BLG is much lower (about 3.8 mM) compared to that of TL (0.5µM ). In addition, the fluorescence lifetime of ANS bound into the cavity of BLG is shorter, about 14 ns.The docking solution that best concurs with experimental data configures the sulfonate group of ANS favorably to interact with the side chains of K114, H84 and E34. The naphthalene group of ANS is in close to L105 of strand G. Comparison of ANS binding to BLG indicates the absence of a positively charged residue corresponding to position K114 of TL. The sulfonate group of ANS has electrostatic interactions with K69 and K60 in BLG. These positively charged residues are located at shallow sites of the BLG calyx compared to K114 of TL. The ANS binding site is located at a deeper position in the calyx of TL than in BLG.

Conclusions: : This study lends credence to the ability of TL to accommodate fatty acids oriented in two opposite directions. The implication is that fatty acids whose carboxyl groups are positioned toward the aqueous phase are available for interaction with TL and could augment stability of the tear film. The charged interaction with the sulfonate group on ANS has implications in exploiting lipocalin drug delivery mechanisms.

Keywords: protein structure/function • lipids • lacrimal gland 

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