Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae

The Biochemical Journal
Roma MukhopadhyayErik T Yukl

Abstract

Bacterial heme nitric oxide/oxygen (H-NOX) domains are nitric oxide (NO) or oxygen sensors. This activity is mediated through binding of the ligand to a heme cofactor. However, H-NOX from Vibrio cholerae (Vc H-NOX) can be easily purified in a heme-free state that is capable of reversibly responding to oxidation, suggesting a heme-independent function as a redox sensor. This occurs by oxidation of Cys residues at a zinc-binding site conserved in a subset of H-NOX homologs. Remarkably, zinc is not lost from the protein upon oxidation, although its ligation environment is significantly altered. Using a combination of computational and experimental approaches, we have characterized localized structural changes that accompany the formation of specific disulfide bonds between Cys residues upon oxidation. Furthermore, the larger-scale structural changes accompanying oxidation appear to mimic those changes observed upon NO binding to the heme-bound form. Thus, Vc H-NOX and its homologs may act as both redox and NO sensors by completely separate mechanisms.

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Apr 3, 2001·Journal of the American Society for Mass Spectrometry·F W McLaffertyB K Carpenter
Mar 5, 2002·Clinical and Diagnostic Laboratory Immunology·Firdausi QadriAnn-Mari Svennerholm
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Qing XuJohn J Mekalanos
Jan 20, 2004·Biochimica Et Biophysica Acta·Shalmoli BhattacharyyaSiddhartha Majumdar
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Patricia PellicenaJohn Kuriyan
Apr 7, 2005·Journal of Inorganic Biochemistry·Elizabeth M Boon, Michael A Marletta
Apr 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Shah M FaruqueJohn J Mekalanos
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Oct 5, 2005·PLoS Pathogens·Nathan S BlowPaula I Watnick
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Apr 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Shah M FaruqueJohn J Mekalanos
Apr 11, 2006·Journal of Computational Chemistry·Dmitri G FedorovMark S Gordon
Jul 1, 1996·Journal of Synchrotron Radiation·N Binsted, S S Hasnain
Nov 17, 2006·Journal of Computational Chemistry·Dmitri G Fedorov, Kazuo Kitaura
Nov 23, 2006·Biochimica Et Biophysica Acta·Leann M MikeshDonald F Hunt
Nov 9, 2007·Biochemistry·Mark S PriceMichael A Marletta
Nov 27, 2008·ACS Chemical Biology·Charles OleaMichael A Marletta
Jan 20, 2009·Bioinformatics·Andrew M WaterhouseGeoffrey J Barton
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·W Kaya ErbilMichael A Marletta
Feb 18, 2010·Protein Science : a Publication of the Protein Society·Charles OleaMichael A Marletta
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yanling WangEdward G Ruby
Jun 25, 2010·Molecular Microbiology·Hans K CarlsonMichael A Marletta
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Alexandra E Purdy, Paula I Watnick
Dec 14, 2011·Journal of the American Society for Mass Spectrometry·Scott R ColeYu Xia
May 15, 2012·Journal of Chemical Theory and Computation·Andreas W GötzRoss C Walker
May 23, 2012·ACS Chemical Biology·Bernadette M HenaresElizabeth M Boon
Jul 19, 2013·The Journal of Biological Chemistry·Claudia M Cremers, Ursula Jakob
Sep 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mark A HerzikMichael A Marletta
Nov 18, 2015·Journal of Chemical Theory and Computation·Chad W HopkinsAdrian E Roitberg
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Sep 10, 2013·Journal of Chemical Theory and Computation·Romelia Salomon-FerrerRoss C Walker
Jun 9, 2009·Journal of Chemical Theory and Computation·M J HarveyG De Fabritiis

❮ Previous
Next ❯

Methods Mentioned

BETA
phosphotransfer profiling
X-ray
size exclusion chromatography
electron capture dissociation

Software Mentioned

R platform
EXAFSPAK
GBSA
EXCURVE
Gamess package
FMO
BLASTP
Chimera
AMBER
SwissProt

Related Concepts

Related Feeds

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.