4JQH

Crystal structure of a new sGC activator (analogue of BAY 58-2667) bound to nostoc H-NOX domain

Summary for 4JQH

• Entry DOI: 10.2210/pdb4jqh/pdb
• Related: 3L6J 4IAE 4IAH 4IAM
• Descriptor: Alr2278 protein, 4-{[(4-carboxybutyl)(2-{2-[(4'-phenoxybiphenyl-4-yl)methoxy]phenyl}ethyl)amino]methyl}benzoic acid, MALONIC ACID, ... (4 entities in total)
• Functional Keywords: guanylyl cyclase, analogue of bay58-2667, signaling protein
• Biological source: Nostoc sp.
• Total number of polymer chains: 2
• Total formula weight: 43830.76

Authors

Kumar, V.,van den Akker, F. (deposition date: 2013-03-20, release date: 2013-11-20, Last modification date: 2024-02-28)

Primary citation

von Wantoch Rekowski, M.,Kumar, V.,Zhou, Z.,Moschner, J.,Marazioti, A.,Bantzi, M.,Spyroulias, G.A.,van den Akker, F.,Giannis, A.,Papapetropoulos, A.
Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics.
J.Med.Chem., 56:8948-8952, 2013

PubMed Abstract: Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of αF helix containing 110-114 residues contributes to the higher activation triggered by 20.

PubMed: 24090476
DOI: 10.1021/jm400539d

Experimental method

X-RAY DIFFRACTION (2.3 Å)