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Combined NMR and computational study for azide binding to human manganese superoxide dismutase

Emmler, T. and Ayala, I. and Silverman, D. and Hafner, S. and Galstyan, A. S. and Knapp, E. W. and Buntkowsky, G. :
Combined NMR and computational study for azide binding to human manganese superoxide dismutase.
[Online-Edition: <Go to ISI>://WOS:000259802400004]
In: Solid State Nuclear Magnetic Resonance, 34 (1-2) pp. 6-13.
[Article] , (2008)

Official URL: <Go to ISI>://WOS:000259802400004

Abstract

Human manganese superoxide dismutase (MnSOD) labeled with 3-fluorotyrosine (Tyf) was complexed with the N-15-labeled inhibitor azide (N-15(3)-). The sample was characterized by solid-state NMR (SSNMR) spectroscopy (F-19-MAS and N-15-CPMAS). Employing F-19-N-15-REDOR spectroscopy, we determined the distances between the fluorine label in Tyrosine-34 and the three N-15-nuclei of the azide and the relative orientation of the azide in the binding pocket of the MnSOD. A distance of R-1 = 4.85 angstrom between the F-19-label of Tyf34 and the nearest N-15 of the azide and an azide-fluorotyrosine Tyf34 angle of 90 degrees were determined. These geometry data are employed as input for molecular modeling of the location of the inhibitor in the active site of the enzyme. In the computations, several possible binding geometries of the azide near the Mn-complex were assumed. Only when the azide replaces the water ligand at the Mn-complex we obtained a geometry of the azide-Mn-complex, which is consistent with the present NMR data. This indicates that the water molecule ligating to the Mn-complex is removed and the azide is placed at this position. As a consequence the azide forms an H bond with Gln143 instead with Tyf34, in contrast to non-F-19-labeled MnSOD, where the azide is hydrogen bonded to the hydroxy group of Tyr34. (C) 2008 Elsevier Inc. All rights reserved.

Item Type: Article
Erschienen: 2008
Creators: Emmler, T. and Ayala, I. and Silverman, D. and Hafner, S. and Galstyan, A. S. and Knapp, E. W. and Buntkowsky, G.
Title: Combined NMR and computational study for azide binding to human manganese superoxide dismutase
Language: German
Abstract:

Human manganese superoxide dismutase (MnSOD) labeled with 3-fluorotyrosine (Tyf) was complexed with the N-15-labeled inhibitor azide (N-15(3)-). The sample was characterized by solid-state NMR (SSNMR) spectroscopy (F-19-MAS and N-15-CPMAS). Employing F-19-N-15-REDOR spectroscopy, we determined the distances between the fluorine label in Tyrosine-34 and the three N-15-nuclei of the azide and the relative orientation of the azide in the binding pocket of the MnSOD. A distance of R-1 = 4.85 angstrom between the F-19-label of Tyf34 and the nearest N-15 of the azide and an azide-fluorotyrosine Tyf34 angle of 90 degrees were determined. These geometry data are employed as input for molecular modeling of the location of the inhibitor in the active site of the enzyme. In the computations, several possible binding geometries of the azide near the Mn-complex were assumed. Only when the azide replaces the water ligand at the Mn-complex we obtained a geometry of the azide-Mn-complex, which is consistent with the present NMR data. This indicates that the water molecule ligating to the Mn-complex is removed and the azide is placed at this position. As a consequence the azide forms an H bond with Gln143 instead with Tyf34, in contrast to non-F-19-labeled MnSOD, where the azide is hydrogen bonded to the hydroxy group of Tyr34. (C) 2008 Elsevier Inc. All rights reserved.

Journal or Publication Title: Solid State Nuclear Magnetic Resonance
Volume: 34
Number: 1-2
Uncontrolled Keywords: manganese super oxide dismutase azide solid-state nmr redor substrate binding f-19-nmr mnsod solid-state nmr double-resonance nmr low-temperature thermochromism molecular torsional angle rotational-echo chemical-shift mas nmr propionibacterium-shermanii distance determinations thermus-thermophilus
Divisions: 07 Fachbereich Chemie > Physical Chemistry
07 Fachbereich Chemie
Date Deposited: 27 Oct 2014 20:39
Official URL: <Go to ISI>://WOS:000259802400004
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356UF Times Cited:3 Cited References Count:83

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