Figure 2. Mechanisms of signal transduction in response to NO· and H₂O₂.

(A) Reduced H-NOX from Shewanella oneidensis with the penta-coordinated heme (yellow) bound to His¹⁰³. (B) Binding of NO· (blue and red spheres) to the H-NOX heme severs the bond between His¹⁰³ and Fe²⁺. Free His¹⁰³ rotates the αF helix (green), activating signal transduction. Recent structures of the H₂O₂ sensor OxyR from Pseudomonas aeruginosa have revealed the molecular mechanism of sensing and signal transduction in response to H₂O₂. (C) Peroxidatic Cys¹⁹⁹ and Cys²⁰⁸ are 15–17Å apart in opposite ends of an α-helix (green). (D) Oxidation of Cys¹⁹⁹ by H₂O₂ produces a sulfenic acid (-SOH) intermediate that is mimicked by a C199D mutation. Oxidation of Cys¹⁹⁹ triggers new hydrogen-bonding interactions between the sulfenylated group and Arg²⁰¹ and Phe²⁰⁰ (not shown). (E) The new hydrogen-bonding disorganizes the intervening α-helix, increasing the reactivity of Cys²⁰⁸ and facilitating formation of a disulfide. (C) and (D) show structures of reduced and OxyR C199D proteins from P. aeruginosa, whereas (E) shows oxidized OxyR from Escherichia coli. PDB codes 4U99, 4U9B, 4Y0M, 4XWS, and 1IBA were used to generate the images in panels (A–E), respectively.