Elucidating the structural and conformational factors responsible for the activity and substrate specificity of alkanesulfonate monooxygenase

Journal of Biomolecular Structure & Dynamics
Valerio FerrarioLucia Gardossi

Abstract

The mechanism and substrate specificity of alkanesulfonate monooxygenase (SsuD) was investigated by combining molecular dynamics simulations, docking, and a comprehensive quantitative structure activity relationships (QSAR) analysis. The FMNH(2) dependent monooxygenase undergoes a dynamic conformational change of the active site, passing from a closed to an open state. As a consequence, substrates have access to the active site and the cofactor is then regenerated by the associated oxidoreductase FMN reductase SsuE.. Computational analysis of the interaction of SsuD with FMNH(2) based on molecular docking and multiple 20 ns molecular dynamics simulations pointed out that the conformational change is mainly driven by salt bridge formation between Arg297 and Glu20 or Asp111. A set of substrates accepted by SsuD were described by means of ALMOND chemical descriptors and a partial least square (PLS) mathematical model was constructed. The PLS model correlates the structure of substrates and enzyme activity, namely kinetic properties (k (cat)/K (M)). Therefore, information coming from the PLS analysis goes beyond the simple ability of the enzyme to recognize the substrate, but includes the factors that affect the capacity of the enz...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Henikoff, J G Henikoff
Jun 1, 1990·Trends in Biochemical Sciences·G K Farber, G A Petsko
Sep 6, 1996·The Journal of Biological Chemistry·A J FisherI Rayment
Jun 1, 1996·Current Opinion in Structural Biology·T Lengauer, M Rarey
Oct 23, 1998·Microbiology·Jan R van der PloegIan F Connerton
Sep 10, 1999·The Journal of Biological Chemistry·E EichhornT Leisinger
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Apr 27, 2000·Journal of Bacteriology·A KahnertM A Kertesz
Aug 2, 2001·Archives of Microbiology·J R van der PloegT Leisinger
Oct 31, 2001·European Journal of Biochemistry·P ChaiyenP Wilairat
Feb 2, 2002·Applied and Environmental Microbiology·Bruno BühlerAndreas Schmid
Nov 26, 2002·Journal of Molecular Biology·Eric EichhornTimothy J Richmond
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Feb 25, 2005·The Journal of Biological Chemistry·Antonello MerlinoFilomena Sica
May 11, 2005·Biochemical and Biophysical Research Communications·Benlian Gao, Holly R Ellis
Oct 21, 2005·Biochemical and Biophysical Research Communications·David P BallouLindsay J Cole
May 23, 2006·Journal of Biotechnology·W J H van BerkelM W Fraaije
Jul 28, 2006·Trends in Biotechnology·Paolo BraiucaLucia Gardossi
Feb 5, 2008·The Journal of Biological Chemistry·Julien ValtonDavid P Ballou
Dec 15, 2010·International Journal of Molecular Sciences·Kyaw Zeyar Myint, Xiang-Qun Xie

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Citations

Jul 26, 2017·Scientific Reports·R Pravin Kumar, Naveen Kulkarni

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Software Mentioned

Grace
MOE
MOE Superpose
Molecular Operating Environment ( MOE )
GRid
MOPAC7
GROMOS
ALMOND
GRIND
GROMACS

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