FixL heme-binding

Figure 5 Structures of the regulatory FG loop of the B. japonicum FixL heme-binding domain (5yFixLH) in the on and off states, as defined by measurements of autophosphorylation (enzymatic Scheme 1, Step 1). The figure shows an overlap of the refined models for both the unliganded on state (light gray), and the cyanide-boimd off state (dark gray), based on the crystal structures of met- and cyanomet-5yFixLH determined to 2.4-A and 2.7-A resolution, respectively. (From Ref 14.)...

A variety of structures have been solved for FixL heme-binding PAS domains (14,53,57). They include the initial crystal structure of the B. japonicum FixL heme-PAS domain in both on (unliganded) and off (cyanide-bound) conformations, as defined by measurements of autophosphorylation (enzymatic Scheme 1, Step 1) (14). The structures of the on Fe and Fe forms of the S. meliloti FixL heme-binding domain and additional off Fe 02 and Fe imidazole forms of the B. japonicum FixL heme-binding domain are also available (53,57). Based on the structures of the ferric unliganded (Fe , or met) and cyanide-bound (Fe CN , or cyanomet) forms of the heme-PAS domains, a small ligand-induced conformational change was postulated to cause the kinase inhibition (14) (Fig. 5). 

Figure 1 The FixL/FixJ two-component regulatory system. In two-component regulatory systems, the inputs and outputs are variable, but the transmitter and receiver domains from unrelated systems share 20% identity. The input of the sensor FixL is a heme-binding domain that inhibits phosphorylation when O2 binds and that permits enzymatic activity when O2 leaves. The output response is transcriptional activation at nitrogen fixation promoters for only hyrpoxic conditions. (From Ref. 36.)...

Figure 7.5. Comparison of the structure of an oxygen detector to that of a light detector. Here, a cartoon structure of the heme-bIndIng region of B. japonicum FixL (dark structure) is compared with that of the light-detecting region of the photoactive yellow protein (pale structure). The dark molecule In the center of the FixL stnjcture is the heme it occurs only in FixL and directly binds to the oxygen. The pale molecule at the bottom of the image is a hydroxycinnamate cofactor that occurs only In the photoactive yellow protein and directly detects light.

Sousa, E.H.S., Tuckerman, J.R., Gonzalez, G., Gilles-Gonzalez, M.A. A memory of oxygen binding explains the dose response of the heme-based sensor FixL. Biochemistry 46, 6249-6257 (2007). doi 10.1021/bi7003334... 

Gilles-Gonzalez MA, Gonzalez G, Perutz MF. Heme-based sensors, exemplified by the kinas FixL, are a new class of heme protein with distinctive ligand binding and autoxidation. Biochemistry 1994 33 8067-8073. 

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