Stigmatellin structure

It was unexpected that the extrinsic domain of Rieske protein was found at different positions in different crystal forms. In bovine structure IQCR (see Table 2), the location of the Rieske extrinsic domain was identified to be close to cytochrome b (Xia et al., 1997). This domain was suggested to have high mobility based on further inhibitor binding experiments and anomalous scattering studies (Kim et al., 1998). In the native chicken bc structure (IBCC), the Rieske domain was found to be far away from haem Ll and close to cytochrome c. However, in the chicken bci complex co-crystallized with Qo site inhibitor stigmatellin (structure 2BCC and 3BCC) the Rieske domain was close to haem Ll and far away from cytochrome Cl, which is approximately the position found in the structure... 

In 2005, the E. A. Berry group published X-ray crystallographic studies of cytochrome bci with bound inhibitors. The structure of PDB 1PP9, resolution 2.23 A, includes stigmatellin A (SMA) in the Qo site and substrate ubiquinone (UQ) in the Qi site, while PDB IPPJ, resolution 2.28 A, includes stigmatellin A in the Qo site and antimycin Ai (ANY) in the Qi site. These... 

Figure 7.30 Comparison of cytochrome bci structures (A) PDB 1PP9 with inhibitor stigmatellin and (B) PDB IPPJ with inhibitors stigmatellin and antimycin A. Visualized using The PyMOL Molecular Graphics System and ChemDraw Ultra, version 10.0. (Printed with permission of Delano Scientific, LLC and CambridgeSoft Corporation.) (See color plate)...

Figure 18-8 Stereoscopic ribbon diagrams of the chicken bc1 complex (A) The native dimer. The molecular twofold axis runs vertically between the two monomers. Quinones, phospholipids, and detergent molecules are not shown for clarity. The presumed membrane bilayer is represented by a gray band. (B) Isolated close-up view of the two conformations of the Rieske protein (top and long helix at right) in contact with cytochrome b (below), with associated heme groups and bound inhibitors, stigmatellin, and antimycin. The isolated heme of cytochrome c, (left, above) is also shown. (C) Structure of the intermembrane (external surface) domains of the chicken bcx complex. This is viewed from within the membrane, with the transmembrane helices truncated at roughly the membrane surface. Ball-and-stick models represent the heme group of cytochrome cy the Rieske iron-sulfur cluster, and the disulfide cysteines of subunit 8. SU, subunit cyt, cytochrome. From Zhang et al.105...

The Qp site was found in a hydrophobic pocket near heme bl, formed by residues from aC, aF, and aef, below acdl, on the intermembrane space side of cytochrome b. No substrate structure in the Qp site has been reported. The site has been characterized using various inhibitors by a number of different research groups. The Qp site inhibitors are spectroscopically divided into two types class I, inhibitors which affect heme b (myxothiazol and MOA type inhibitors) class II, inhibitors which affect both heme bn and FeS cluster [stigmatellin, UBDBT [5-undecyl-6-hydroxy-4,7-dioxobenzothiazol).] We have succeeded in obtaining a class I inhibitor structure (myxothiazol) however, we were... 

Fig. 9. Three different conformations of ISP in relation to its neighbors. (A) Structure in the c form. An inhibitor, myxothiazol, bound to the Qp site is also shown. (B) Structure in Inf form. (C) Structure in the b form. An inhibitor, stigmatellin, bound to the Qp site is also shown.

Other recent reports further confirmed the different locations occupied by the extrinsic [2Fe 2S] domain in different crystals. An intermediate location was reported by Iwata et alf in a new crystal form which places this domain 27.5 A from Cyt ci and 13 A from the Qo site. Kim, (D) Xia, (C-A) Yu, (J-Z) Xia, Kachurin, Zhang, (L) Yu and Deisenhofer further examined crystal stmctures of bovine mitochondrial Cyt-bc complexes with inhibitors bound to the Qo and/or Qj (j.e., Q ) sites. Binding of the Qq-site inhibitor UHDBT (5-undecyl-6-hydroxy-4,7-dioxobenzothiazol) and stigmatellin was found to result in the [2Fe 2S] domain being at the Cyt b interface, whereas binding of myxothiazol or MOAS (methoxyacrylate-stilbene) led to the release of this domain. The native complex with a vacant Qo site was found to have a structure intermediate between these two extremes. 

Figure 14 X-ray crystal structures of cytochrome bc from chicken in the presence of stigmatellin and antimycm (h state), and in the beef P6s22 crystals (ci state).The Rieske, cyt ci, and cyt b subunits are colored blue, green, and grey, respectively. The hemes, the 2Fe2S center, stigmatelUn, and antimycm are colored red, red/yellow, cyan, and green, respectively. The Rieske neck region residues 66-72 are colored orange, the ef loop is yellow, and EIisl61 is colored purple...

Figure 8.13. Yeast cytochrome bci stereo view of the membrane-bound ligands—hemes bt and bn, stigmatellin occupying the Q (ubiquinol) site, and ubiquinone at the Qi site. (A) Ball and stick representation to show molecular backbone structures. (B) Space-filling representation to give proper volume representation. By means of AG,p, ubiquinol, on becoming positively charged by oxidation at the Qo site, opens an aqueous channel to the cytoplasmic...

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