Cofactor assisted gating mechanism in the active site of NADH oxidase from Thermus thermophilus

Proteins
Jozef HritzErik Sedlák

Abstract

NADH oxidase (NOX) from Thermus thermophilus is a member of a structurally homologous flavoprotein family of nitroreductases and flavin reductases. The importance of local conformational dynamics in the active site of NOX has been recently demonstrated. The enzyme activity was increased by 250% in the presence of 1 M urea with no apparent perturbation of the native structure of the protein. The present in silico results correlate with the in vitro data and suggest the possible explanation about the effect of urea on NOX activity at the molecular level. Both, X-ray structure and molecular dynamics (MD) simulations, show open conformation of the active site represented by approximately 0.9 nm distance between the indole ring of Trp47 and the isoalloxazine ring of FMN412. In this conformation, the substrate molecule can bind in the active site without sterical restraints. MD simulations also indicate more stable conformation of the active site called "closed" conformation. In this conformation, Trp47 and the isoalloxazine ring of FMN412 are so close to each other (approximately 0.5 nm) that the substrate molecule is unable to bind between them without perturbing this conformation. The open/close transition of the active site betwe...Continue Reading

References

Aug 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·J A McCammon, M Karplus
Jun 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·B R Gelin, M Karplus
Oct 18, 1990·Nature·M Karplus, G A Petsko
Jan 1, 1988·Advances in Protein Chemistry·S K Burley, G A Petsko
Feb 14, 1971·Journal of Molecular Biology·B Lee, F M Richards
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 1, 1995·Nature Structural Biology·H J HechtR D Schmid
Oct 22, 1996·Biochemistry·J J TannerK L Krause
Sep 23, 1997·Biochemical and Biophysical Research Communications·H J ZhangJ M Zhou
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·H X ZhouJ A McCammon
Apr 27, 1992·Physical Review Letters·A E García
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Dec 22, 1999·Biochemical and Biophysical Research Communications·T InuiO Hayaishi
May 24, 2001·The Journal of Biological Chemistry·P A HubbardJ J Kim
Jan 24, 2002·The Journal of Biological Chemistry·Chad A HaynesDavid W Rodgers
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Peter J WinnRebecca C Wade
Jun 19, 2002·Accounts of Chemical Research·Tongye ShenJ Andrew McCammon
Dec 5, 2003·European Journal of Biochemistry·Gabriel ZoldákErik Sedlák
Apr 14, 2004·The Journal of Biological Chemistry·Aileen E BoydDavid A Johnson
Mar 5, 2005·Anti-cancer Drugs·Gabi U DachsGillian M Tozer

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Citations

Sep 29, 2011·Journal of Biomolecular NMR·Teresa MilettiAnthony Mittermaier
May 15, 2015·Protein Science : a Publication of the Protein Society·Teresa MilettiAnthony Mittermaier
Apr 27, 2013·Chemical Reviews·Artur GoraJiri Damborsky

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