3QJ5

S-nitrosoglutathione reductase (GSNOR) in complex with N6022

Summary for 3QJ5

• Entry DOI: 10.2210/pdb3qj5/pdb
• Descriptor: Alcohol dehydrogenase class-3, ZINC ION, POTASSIUM ION, ... (9 entities in total)
• Functional Keywords: s-nitrosoglutathione reductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P11766
• Total number of polymer chains: 2
• Total formula weight: 83095.25

Authors

Chun, L.,Kim, H.,Sun, X. (deposition date: 2011-01-28, release date: 2011-04-06, Last modification date: 2024-04-03)

Primary citation

Sun, X.,Wasley, J.W.,Qiu, J.,Blonder, J.P.,Stout, A.M.,Green, L.S.,Strong, S.A.,Colagiovanni, D.B.,Richards, J.P.,Mutka, S.C.,Chun, L.,Rosenthal, G.J.
Discovery of s-nitrosoglutathione reductase inhibitors: potential agents for the treatment of asthma and other inflammatory diseases.
ACS Med Chem Lett, 2:402-406, 2011

PubMed Abstract: S-Nitrosoglutathione reductase (GSNOR) regulates S-nitrosothiols (SNOs) and nitric oxide (NO) in vivo through catabolism of S-nitrosoglutathione (GSNO). GSNOR and the anti-inflammatory and smooth muscle relaxant activities of SNOs, GSNO, and NO play significant roles in pulmonary, cardiovascular, and gastrointestinal function. In GSNOR knockout mice, basal airway tone is reduced and the response to challenge with bronchoconstrictors or airway allergens is attenuated. Consequently, GSNOR has emerged as an attractive therapeutic target for several clinically important human diseases. As such, small molecule inhibitors of GSNOR were developed. These GSNOR inhibitors were potent, selective, and efficacious in animal models of inflammatory disease characterized by reduced levels of GSNO and bioavailable NO. N6022, a potent and reversible GSNOR inhibitor, reduced bronchoconstriction and pulmonary inflammation in a mouse model of asthma and demonstrated an acceptable safety profile. N6022 is currently in clinical development as a potential agent for the treatment of acute asthma.

PubMed: 24900320
DOI: 10.1021/ml200045s

Experimental method

X-RAY DIFFRACTION (1.9 Å)