Figure 7.

(A) Docking results of L11–RNA–thiostrepton. The bundle of the 10 best docking results from the top-ranked HADDOCK cluster is shown for the docking of L11 (blue), RNA (red) and thiostrepton (green) on the left. A combined ribbon/surface diagram for the best representative of the predominant docking orientation (same orientation as the bundle) is shown on the right. The side-chains of the RNA A1067, A1095 and the L11 24–36 residues are indicated by bold sticks. AIRs are defined for the interaction surface of L11_ctd and the RNA (L11 residues: 74–76, 80, 87–94, 112, 115–119, 123, 126, 127, 130, 131, 133–135 and RNA nucleotides: 1058–1060, 1062–1065, 1075–1083 and 1088). For the binding of thiostrepton to the RNA, ambiguous restraints have been defined that are based on NOE data (53) for specific protons of the thiostrepton (thr-2, tzb-3 and tsi-4) to the H2, H8 and H1′ protons of any adenosine and cytosine within or near the binding pocket (nucleotides A:1067, 1069, 1070, 1073, 1095, 1096, 1098 and C: 1097 and 1100). Two AIRs were defined based on mutational analysis (47) for A1067 and A1095 to thiostrepton. L11_ntd residues 11, 12, 24, 28, 29, 33, 36 and 56 have been selected as active restraints to either thiostrepton or the RNA (1059–1064, 1068–1070 and 1095–1098). Residues 9–14, 21–37, 39, 40, 53, 55–57, 74 of L11 have been defined as passive restraints for the interaction with thiostrepton. (B) Model for L11 binding to RNA and thiostrepton. The L11 (blue) domain orientation changes upon binding to the 23S RNA region (red) and the thiostrepton antibiotic (green). The interaction specifically influences the dynamical properties of both domains.