title: S-Nitrosylation Induces Structural and Dynamical Changes in a Rhodanese Family Protein.
abstract: S-Nitrosylation is well established as an important post-translational regulator in protein function and signaling. However, relatively little is known about its structural and dynamical consequences. We have investigated the effects of S-nitrosylation on the rhodanese domain of the Escherichia coli integral membrane protein YgaP by NMR, X-ray crystallography, and mass spectrometry. The results show that the active cysteine in the rhodanese domain of YgaP is subjected to two competing modifications: S-nitrosylation and S-sulfhydration, which are naturally occurring in vivo. It has been observed that in addition to inhibition of the sulfur transfer activity, S-nitrosylation of the active site residue Cys63 causes an increase in slow motion and a displacement of helix 5 due to a weakening of the interaction between the active site and the helix dipole. These findings provide an example of how nitrosative stress can exert action at the atomic level.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Eichmann
authors.affiliation: Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Tzitzilonis
authors.affiliation: Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Witek
authors.initials: W
authors.lastname: Kwiatkowski
authors.affiliation: Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Innokentiy
authors.initials: I
authors.lastname: Maslennikov
authors.affiliation: Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Senyon
authors.initials: S
authors.lastname: Choe
authors.affiliation: Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA; Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland; Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: roland.riek@phys.chem.ethz.ch.
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013884:Thiosulfate Sulfurtransferase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C530142:YgaP protein, E coli; D013884:Thiosulfate Sulfurtransferase; D003545:Cysteine
keywords: X-ray crystallography; mass spectrometry; nuclear magnetic resonance (NMR); post-translational modification; rhodanese