Premium
Suramin Distinguishes Between the Calmodulin Binding Sequences of Inducible and Neuronal Nitric Oxide Synthase
Author(s) -
Sweda Nicholas,
McNamara Alyssa,
StevensTruss Regina
Publication year - 2013
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.27.1_supplement.560.15
Subject(s) - suramin , nitric oxide synthase , gene isoform , calmodulin , nitric oxide , enzyme , chemistry , biochemistry , nos1 , microbiology and biotechnology , pharmacology , biology , in vitro , gene , organic chemistry
Nitric oxide synthase (NOS) catalyzes the production of nitric oxide (•NO) from L‐arginine in several tissues in the body. Nitric oxide is believed to play a critical role in cardiovascular disease, stroke, and cancer. For this reason, selective inhibition of NOS isoforms is currently under investigation for their potential as targets in drug design. All known isoforms of NOS require binding of calmodulin (CaM), a calcium binding protein ubiquitously expressed in eukaryotes, for activity. The interactions among the NOS isoforms and CaM vary, and therefore pose a good place to study in differentiating these enzymes. We have previously demonstrated that suramin, a polysulfonated naphthylurea, can distinguish between the CaM binding region of the inducible NOS and the neuronal NOS. When bound to NOS, suramin inhibits its activity by preventing CaM binding and activation. Suramin's inhibition was found not to be time dependent, and IC 50 values were found to be ~8 μM and ~120 μM for the inducible NOS and neuronal NOS, respectively. SDS‐PAGE and Western analyses demonstrated that suramin is able to inhibit the interaction between NOS and CaM. AutoDoc analysis further demonstrated that suramin most likely interacts with a portion of the NOS molecule believed to be crucial to CaM's interaction. These studies implicate suramin as a potential lead compound.