4ioa | pdb_00004ioa
Crystal structure of compound 4e bound to large ribosomal subunit (50S) from Deinococcus radiodurans
Structural highlights
Function[RL15_DEIRA] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341_B] [RL25_DEIRA] This is one of 3 proteins that mediate the attachment of the 5S rRNA onto the large ribosomal subunit. This protein has three domains. The N-terminal one is bound on the solvent face, the middle domain fills the space between the 5S rRNA and the L11 arm contacting the 23S rRNA while the C-terminal domain is on the edge of the intersubunit interface and contacts the A site. The protein conformation changes upon binding of a tRNA mimic to the A site, although the mimic does not interact directly with CTC itself, consistent with CTCs presumed role in moderating A site binding.[HAMAP-Rule:MF_01334] [RL6_DEIRA] 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). This protein binds to the 23S rRNA, and is important in its secondary structure.[HAMAP-Rule:MF_01365] [RL32_DEIRA] Forms a cluster with L17 and L22, and with L22, a pair of "tweezers" that hold together all the domains of the 23S rRNA. Interacts with the antibiotic troleandomycin which blocks the peptide exit tunnel.[HAMAP-Rule:MF_00340] [RL21_DEIRA] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_01363] [RL27_DEIRA] Binds the 5S and 23S rRNAs and also the tRNA in the P site.[HAMAP-Rule:MF_00539] [RL22_DEIRA] 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).[HAMAP-Rule:MF_01331_B] The globular domain of the protein is located by the polypeptide exit tunnel on the outside of the subunit while an extended beta-hairpin forms part of the wall of the tunnel. Forms a pair of "tweezers" with L32 that hold together two different domains of the 23S rRNA. Interacts with the tunnel-blocking modified macrolide azithromycin. Upon binding of the macrolide troleadomycin to the ribosome, the tip of the beta-hairpin is displaced, which severely restricts the tunnel. This and experiments in E.coli have led to the suggestion that it is part of the gating mechanism involved in translation arrest in the absence of the protein export system.[HAMAP-Rule:MF_01331_B] [RL36_DEIRA] Binds the 23S rRNA.[HAMAP-Rule:MF_00251] [RL20_DEIRA] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_00382] [RL17_DEIRA] Binds to the 23S rRNA.[HAMAP-Rule:MF_01368] [RL35_DEIRA] Binds the 23S rRNA.[HAMAP-Rule:MF_00514] [RL33_DEIRA] Binds the 23S rRNA and the E site tRNA.[HAMAP-Rule:MF_00294] [RL30_DEIRA] Binds the 5S and 23S rRNAs.[HAMAP-Rule:MF_01371] [RL5_DEIRA] 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 (bridge B1b), connecting the 2 subunits; this bridge is implicated in subunit movement (By similarity). Contacts the P site tRNA; the 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs.[HAMAP-Rule:MF_01333_B] [RL34_DEIRA] Binds the 23S rRNA.[HAMAP-Rule:MF_00391] [RL2_DEIRA] 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).[HAMAP-Rule:MF_01320_B] [RL13_DEIRA] This protein is one of the early assembly proteins of the 50S ribosomal subunit (By similarity). Binds to the 23S rRNA.[HAMAP-Rule:MF_01366_B] [RL16_DEIRA] Binds the 5S and 23S rRNAs and is also seen to make contacts with the A and P site tRNAs. Interacts with A site tRNA mimics, and is probably one of the key factors, along with a helix of the 23S rRNA, in positioning tRNA stems in the peptidyl-transferase center.[HAMAP-Rule:MF_01342] [RL24_DEIRA] 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 (By similarity).[HAMAP-Rule:MF_01326_B] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Contacts trigger factor (TF) when it is bound to the ribosome; this contact may expose a hydrophobic crevice in TF (PubMed:16271892).[HAMAP-Rule:MF_01326_B] [RL18_DEIRA] This is one of the proteins that binds and mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance.[HAMAP-Rule:MF_01337_B] [RL19_DEIRA] This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity). Binds the 23S rRNA.[HAMAP-Rule:MF_00402] [RL11_DEIRA] This protein binds directly to 23S ribosomal RNA and also contacts the CTC protein (RL25).[HAMAP-Rule:MF_00736_B] [RL3_DEIRA] 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).[HAMAP-Rule:MF_01325_B] [RL29_DEIRA] Binds the 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_00374] [RL14_DEIRA] Forms part of two intersubunit bridges in the 70S ribosome (By similarity). Binds to 23S rRNA.[HAMAP-Rule:MF_01367] [RL23_DEIRA] One of the early assembly protein (By similarity) it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Forms the main docking site for trigger factor binding to the ribosome (PubMed:16091460 and PubMed:16271892).[HAMAP-Rule:MF_01369] [RL4_DEIRA] 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 (By similarity).[HAMAP-Rule:MF_01328_B] Makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit.[HAMAP-Rule:MF_01328_B] This protein is located close to the polypeptide exit tunnel, and interacts with the modified macrolide azithromycin, which blocks the tunnel.[HAMAP-Rule:MF_01328_B] Publication Abstract from PubMedA novel series of 3-O-carbamoyl erythromycin A derived analogs, labeled carbamolides, with activity versus resistant bacterial isolates of staphylococci (including macrolide and oxazolidinone resistant strains) and streptococci are reported. An (R)-2-aryl substituent on a pyrrolidine carbamate appeared to be critical for achieving potency against resistant strains. Crystal structures showed a distinct aromatic interaction between the (R)-2-aryl (3-pyridyl for 4d) substituent on the pyrrolidine and G2484 (G2505, Escherichia coli) of the Deinococcus radiodurans 50S ribosome (3.2A resolution). Novel 3-O-carbamoyl erythromycin A derivatives (carbamolides) with activity against resistant staphylococcal and streptococcal isolates.,Magee TV, Han S, McCurdy SP, Nguyen TT, Granskog K, Marr ES, Maguire BA, Huband MD, Chen JM, Subashi TA, Shanmugasundaram V Bioorg Med Chem Lett. 2013 Mar 15;23(6):1727-31. doi: 10.1016/j.bmcl.2013.01.067., Epub 2013 Jan 26. PMID:23414806[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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