Premium
NITRIC OXIDE SIGNALING IN BLOOD‐SUCKING INSECTS, HORNWORMS AND HUMANS
Author(s) -
Montfort William R.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.318.3
Subject(s) - heme , nitric oxide , transmembrane protein , thioredoxin , soluble guanylyl cyclase , chemistry , microbiology and biotechnology , biochemistry , gucy1a3 , cell signaling , cytosol , receptor , biophysics , signal transduction , biology , guanylate cyclase , guanylate cyclase 2c , oxidative stress , organic chemistry , enzyme
We are investigating the molecular mechanisms underlying the wonderful biology of nitric oxide signaling using ultra‐high resolution X‐ray crystallography, rapid transient kinetic measurements, spectroscopy and model cellular systems. Our studies include both heme‐based NO carriers and sensors, cytosolic proteins involved in S‐nitrosation, and transmembrane proteins of importance in transmitting regulatory signals from outside to inside the cell. We have been particularly successful with the nitrophorins, NO transport proteins from the kissing bug and the bed bug, soluble guanylyl cyclase (sGC) from the tobacco hornworm, human thioredoxin and transmembrane protein CD47, which may be a non‐canonical G‐protein coupled receptor. Here, I will describe our efforts to understand both NO‐dependent and independent regulation of sGC, the primary heme‐based NO receptor in animals, and how this relates to the conformational dynamics displayed by the nitrophorins. I will also describe how binding of benzylindazole‐related compounds such as YC‐1 to sGC alters the heme environment, serving to trap NO and CO gas molecules in the pocket through geminate recombination. YC‐1 and related compounds act both independently and synergistically with NO and CO binding and provide a new path for the discovery of drugs targeted to cardiovascular disease.