3LAI

Structural insights into the molecular mechanism of H-NOX activation

Summary for 3LAI

• Entry DOI: 10.2210/pdb3lai/pdb
• Related: 1U4H 1U55 1U56 3EEE 3IQB 3LAH
• Descriptor: Methyl-accepting chemotaxis protein, PROTOPORPHYRIN IX CONTAINING FE, IMIDAZOLE, ... (4 entities in total)
• Functional Keywords: signaling protein
• Biological source: Thermoanaerobacter tengcongensis
• Total number of polymer chains: 3
• Total formula weight: 68163.19

Authors

Olea Jr, C.,Herzik Jr, M.A.,Kuriyan, J.,Marletta, M.A. (deposition date: 2010-01-06, release date: 2010-03-16, Last modification date: 2023-09-06)

Primary citation

Olea, C.,Herzik, M.A.,Kuriyan, J.,Marletta, M.A.
Structural insights into the molecular mechanism of H-NOX activation.
Protein Sci., 19:881-887, 2010

PubMed Abstract: Nitric oxide (NO) signaling in mammals controls important processes such as smooth muscle relaxation and neurotransmission by the activation of soluble guanylate cyclase (sGC). NO binding to the heme domain of sGC leads to dissociation of the iron-histidine (Fe-His) bond, which is required for enzyme activity. The heme domain of sGC belongs to a larger class of proteins called H-NOX (Heme-Nitric oxide/OXygen) binding domains. Previous crystallographic studies on H-NOX domains demonstrate a correlation between heme bending and protein conformation. It was unclear, however, whether these structural changes were important for signal transduction. Subsequent NMR solution structures of H-NOX proteins show a conformational change upon disconnection of the heme and proximal helix, similar to those observed in the crystallographic studies. The atomic details of these conformational changes, however, are lacking in the NMR structures especially at the heme pocket. Here, a high-resolution crystal structure of an H-NOX mutant mimicking a broken Fe-His bond is reported. This mutant exhibits specific changes in heme conformation and major N-terminal displacements relative to the wild-type H-NOX protein. Fe-His ligation is ubiquitous in all H-NOX domains, and therefore, the heme and protein conformational changes observed in this study are likely to occur throughout the H-NOX family when NO binding leads to rupture of the Fe-His bond.

PubMed: 20162612
DOI: 10.1002/pro.357

Experimental method

X-RAY DIFFRACTION (2.144 Å)