6cfj | pdb_00006cfj

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Crystal structure of the Thermus thermophilus 70S ribosome in complex with histidyl-CAM and bound to mRNA and A-, P-, and E-site tRNAs at 2.8A resolution

spinqualitylabelsall models 6cfj, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cfj is a 112 chain structure with sequence from Thet8 and Thermus thermophilus (strain hb8 / atcc 27634 / dsm 579). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EZG, K, MG, SF4, ZN NonStd Res: 0TD, 2MA, 2MG, 2MU, 4OC, 4SU, 5MC, 5MU, 7MG, M2G, MA6, MIA, OMG, PSU, UNK, UR3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Warning: this is a large structure, and loading might take a long time or not happen at all. Function [RS2_THET2] Spans the head-body hinge region of the 30S subunit. Is loosely associated with the 30S subunit (By similarity). [RL25_THET2] This is one of the proteins that binds to the 5S RNA in the ribosome where it forms part of the central protuberance (By similarity). [RL6_THETH] This protein binds to the 23S rRNA, and is important in its secondary structure. It is located near the subunit interface in the base of the L7/L12 stalk, and near the tRNA binding site of the peptidyltransferase center (By similarity).[HAMAP-Rule:MF_01365] [RL31_THET2] Binds the 23S rRNA (By similarity). [RL21_THET2] This protein binds to 23S rRNA in the presence of protein L20 (By similarity). [RL22_THETH] This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g. L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity). The globular domain of the protein is one of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that penetrates into the center of the 70S ribosome. This extension seems to form part of the wall of the exit tunnel (By similarity). Deleting residues 82 to 84 (the equivalent deletion in E.coli renders cells resistant to erythromycin) would probably cause the tip of the hairpin to penetrate into the tunnel. [RL20_THET2] Binds directly to 23S ribosomal RNA and is necessary for the in vitro assembly process of the 50S ribosomal subunit. It is not involved in the protein synthesizing functions of that subunit (By similarity). [RS13_THET2] Located at the top of the head of the 30S subunit, it contacts several helices of the 16S rRNA. In the 70S ribosome it contacts the 23S rRNA (bridge B1a) and protein L5 of the 50S subunit (bridge B1b), connecting the 2 subunits; these bridges are implicated in subunit movement. Contacts the tRNAs in the A and P-sites (By similarity). [RL32_THET8] Found on the solvent side of the large subunit.[HAMAP-Rule:MF_00340] [RS9_THET8] Part of the top of the head of the 30S subunit. The C-terminal region penetrates the head emerging in the P-site where it contacts tRNA.[HAMAP-Rule:MF_00532_B] [RL24_THETH] One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. [RL18_THETH] This is one of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance (By similarity). [RS18_THET2] Binds as a heterodimer with protein S6 to the central domain of the 16S rRNA, where it helps stabilize the platform of the 30S subunit (By similarity). [RL14_THET8] This protein binds directly to 23S ribosomal RNA (By similarity).[HAMAP-Rule:MF_01367] Contacts the 16S rRNA of the 30S subunit in two different positions helping to form bridges B5 and B8.[HAMAP-Rule:MF_01367] [RS4_THET2] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the body and platform of the 30S subunit (By similarity). [RL15_THETH] Binds to the 23S rRNA (By similarity). [RS17_THET8] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the platform and body of the 30S subunit by bringing together and stabilizing interactions between several different RNA helices. The combined cluster of proteins S8, S12 and S17 appears to hold together the shoulder and platform of the 30S subunit.[HAMAP-Rule:MF_01345] Deletion of the protein leads to an increased generation time and a temperature-sensitive phenotype.[HAMAP-Rule:MF_01345] [RS11_THET2] Located on the upper part of the platform of the 30S subunit, where it bridges several disparate RNA helices of the 16S rRNA. Forms part of the Shine-Dalgarno cleft in the 70S ribosome (By similarity). [RL27_THET8] Found on the solvent side of the large subunit.[HAMAP-Rule:MF_00539] [RS15_THETH] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the platform of the 30S subunit by binding and bridging several RNA helices of the 16S rRNA. Forms an intersubunit bridge (bridge B4) with the 23S rRNA of the 50S subunit in the ribosome (By similarity). [RL34_THET8] Found on the solvent side of the large subunit.[HAMAP-Rule:MF_00391] [RL5_THETH] This is 1 of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance. In the 70S ribosome it contacts protein S13 of the 30S subunit (forming bridge B1b) connecting the head of the 30S subunit to the top of the 50S subunit. The bridge itself contacts the P site tRNA and is implicated in movement during ribosome translocation. Also contacts the P site tRNA independently of the intersubunit bridge; the 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs (By similarity).[HAMAP-Rule:MF_01333_B] [RS19_THETH] Protein S19 forms a complex with S13 that binds strongly to the 16S ribosomal RNA (By similarity). [RS8_THETH] One of the primary rRNA binding proteins, it binds directly to 16S rRNA central domain where it helps coordinate assembly of the platform of the 30S subunit (By similarity). [RS5_THETH] With S4 and S12 plays an important role in translational accuracy (By similarity).[HAMAP-Rule:MF_01307_B] Located at the back of the 30S subunit body where it stabilizes the conformation of the head with respect to the body (By similarity).[HAMAP-Rule:MF_01307_B] [RL2_THET2] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome (By similarity). [RS20_THET8] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the bottom of the body of the 30S subunit, by binding to several RNA helices of the 16S rRNA.[HAMAP-Rule:MF_00500] [RL13_THET2] This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly (By similarity). [RS10_THETH] Involved in the binding of tRNA to the ribosomes (By similarity). [RL16_THET8] This protein binds directly to 23S rRNA. Interacts with the A site tRNA.[HAMAP-Rule:MF_01342] [RS16_THET2] Binds to the lower part of the body of the 30S subunit, where it stabilizes two of its domains (By similarity). [RL19_THET8] Contacts the 16S rRNA of the 30S subunit (part of bridge B6), connecting the 2 subunits.[HAMAP-Rule:MF_00402] [RSHX_THETH] Binds at the top of the head of the 30S subunit. It stabilizes a number of different RNA elements and thus is important for subunit structure (By similarity). [RS7_THET2] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to the decoding center, probably blocks exit of the E-site tRNA (By similarity). [RL9_THET8] Binds to the 23S rRNA. Extends more that 50 Angstroms beyond the surface of the 70S ribosome.[HAMAP-Rule:MF_00503] [RL3_THETH] One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit (By similarity). [RS3_THET2] Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation (By similarity). [RS14Z_THETH] Binds 16S rRNA, required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site (By similarity). [RS6_THETH] Located on the outer edge of the platform on the body of the 30S subunit (By similarity). [RS12_THETH] With S4 and S5 plays an important role in translational accuracy (By similarity).[HAMAP-Rule:MF_00403_B] Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Located at the interface of the 30S and 50S subunits, it traverses the body of the 30S subunit contacting proteins on the other side and probably holding the rRNA structure together. The combined cluster of proteins S8, S12 and S17 appears to hold together the shoulder and platform of the 30S subunit (By similarity).[HAMAP-Rule:MF_00403_B] [RL23_THETH] One of the early assembly proteins it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the ribosome. Forms the main docking site for trigger factor binding to the ribosome (By similarity). [RL4_THET8] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity).[HAMAP-Rule:MF_01328_B] Forms part of the polypeptide exit tunnel (By similarity).[HAMAP-Rule:MF_01328_B] This protein can be incorporated into E.coli ribosomes in vivo, which resulted in decreased peptidyltransferase (Ptase) activity of the hybrid ribosomes. The hybrid 50S subunits associate less well with 30S subunits to form the ribosome.[HAMAP-Rule:MF_01328_B] Publication Abstract from PubMed Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amino acid analogs of CHL. The L-histidyl analog binds to the ribosome with the affinity exceeding that of CHL by 10 fold. Several of the newly synthesized analogs were able to inhibit protein synthesis and exhibited the mode of action that was distinct from the action of CHL. However, the inhibitory properties of the semi-synthetic CHL analogs did not correlate with their affinity and in general, the amino acid analogs of CHL were less active inhibitors of translation in comparison with the original antibiotic. The X-ray crystal structures of the Thermus thermophilus 70S ribosome in complex with three semi-synthetic analogs showed that CHL derivatives bind at the peptidyl transferase center, where the aminoacyl moiety of the tested compounds established idiosyncratic interactions with rRNA. Although still fairly inefficient inhibitors of translation, the synthesized compounds represent promising chemical scaffolds that target the peptidyl transferase center of the ribosome and potentially are suitable for further exploration. Binding and Action of Amino Acid Analogs of Chloramphenicol upon the Bacterial Ribosome.,Tereshchenkov AG, Dobosz-Bartoszek M, Osterman IA, Marks J, Sergeeva VA, Kasatsky P, Komarova ES, Stavrianidi AN, Rodin IA, Konevega AL, Sergiev PV, Sumbatyan NV, Mankin AS, Bogdanov AA, Polikanov YS J Mol Biol. 2018 Feb 2. pii: S0022-2836(18)30042-1. doi:, 10.1016/j.jmb.2018.01.016. PMID:29410130 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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