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Chapter 6 : Antibiotics That Block Protein Synthesis

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Antibiotics That Block Protein Synthesis, Page 1 of 2

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Abstract:

To date, more than 2,500 bacterial genomes have been sequenced, and genome sizes are found to range from 3 to 9 megabases of DNA, with very little noncoding DNA. Assuming a typical size of encoded proteins of about 30,000 to 35,000 daltons (found in , for example), then an average protein may have 300 residues, representing around 1 kilobase of DNA. Thus, the coding capacity of bacterial cells may be in the range of 3,000 to 9,000 proteins. Some proteins that function in primary metabolic pathways such as energy metabolism, information transfer, and membrane formation are expressed constitutively, while many others, including permeases and enzymes that allow growth on facultative energy sources, are upregulated in response to specific signals. Disruption of protein synthesis machinery in bacteria by antibiotics that target these processes is initially bacteriostatic and can be bactericidal depending on other stresses to the bacteria.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Figures

Image of Figure 6.0
Figure 6.0

Snapshot of the 70S ribosome (PDB for 50S is 2WDL; PDB for 30S and tRNAs is 2WDK) bound to three classes of antibiotics. The figure shows RNA (gray) and protein (yellow) components of the ribosome with associated tRNAs shown as blue cartoons and bound antibiotics shown as red space filling spheres. The terpenoid tiamulin binds to the 23S rRNA at the peptidyltransferase center (PDB 1XBP). The nonribosomal peptide viomycin binds at the interface of the 50S and 30S subunits at the tRNA A site (PDB 4V7L). The thiazolyl peptide thiostrepton binds at the periphery, interacting with a specific pair of 23S rRNA helices and a proline-rich region of the L11 protein subunit (PDB 3CF5). This chapter is primarily dedicated to revealing the molecular details of how small-molecule antibiotics interact with various “hot spots” on the massive macromolecular bacterial ribosome and is intended to complement the comprehensive review article from Wilson (2009). (Image created using PyMOL).

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.1
Figure 6.1

(a) DNA is transcribed into mRNA by RNA polymerase, and the coded mRNA is translated into protein by the ribosome. Both RNA polymerase (taken up in chapter 7) and the ribosome (taken up in this chapter) are proven antibiotic targets. (b) The 70S ribosome uses an mRNA template and complementing aminoacyl-tRNAs as adaptors to synthesize proteins with high fidelity.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.2
Figure 6.2

Anatomy of a bacterial ribosome: the large (50S) and small (30S) subunits are depicted, as is the path of an mRNA molecule as template; the binding of aminoacylated tRNAs at the aminoacyl (A), peptidyl (P), and exit (E) sites; and the exit tunnel for the growing polypeptide chain.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.3
Figure 6.3

Schematic overview of ribosomal bacterial protein synthesis, depicting initiation, accommodation, elongation, and termination events. Peptidyl transfer (chain elongation) occurs as the growing chain moves from the tRNA in the P site to the aminoacyl-tRNA in the A site. That peptidyl-tRNA then has to be translocated to the P site for the subsequent cycle of elongation.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.4
Figure 6.4

Anatomy of a charged Phe-tRNA. The triplet anticodon region is highlighted at the bottom of the structure in red. The terminal 3′-A residue is shown in red, with an attached 3′--Phe amino acid residue in blue.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.5
Figure 6.5

(a) Structure of mupirocin, a polyketide antibiotic that selectively inhibits bacterial isoleucyl-tRNA synthetase. (b) Mupirocin bound to isoleucyl-tRNA synthetase with the nonanic acid ester curled to the left in the active site. (Image generated using PyMOL from PDB 1JZS [Nakama et al., 2001; Thomas et al., 2010].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.6
Figure 6.6

Two-step mechanism for amino acid selection and activation by aminoacyl-tRNA synthetases: (a) formation of aminoacyl-AMP by carboxylate attack on α-phosphate of ATP; (b) transfer of activated aminoacyl group to 3′-OH of the ribose at the CCA end of a cognate tRNA. See Fig. 6.4 for three-dimensional representation of a 3′--aminoacyl-tRNA.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.7
Figure 6.7

Seven structurally diverse inhibitors of selected bacterial aminoacyl-tRNA synthetases. All of the molecules are natural products except for CB432.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.8
Figure 6.8

Binding sites for a variety of antibiotics on the 30S and 50S subunits of the ribosome. (a) A view of the 70S ribosome with E, P, and A tRNAs and bound antibiotics shown as space-filling spheres. (b and c) Close-up views of clustered antibiotics in the PTC. (d) A close-up view of antibiotics clustered on the 30S ribosomal subunit. See Table 6.1 for antibiotic abbreviations and PDB files used to create the PyMOL images in panels a to d.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.9
Figure 6.9

Peptide bond formation between aminoacyl-tRNA and peptidyl-tRNA at the PTC in the 50S subunit of the ribosome.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.10
Figure 6.10

Schematic of the exit tunnel for the nascent peptide chain as it passes through and exits the ribosome channel. (Figure created from a cross section of overlaid PDB files 2WDK and 2WDL with tRNAs in the E, P, and A sites.)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.11
Figure 6.11

Antibiotics that block the phase of protein synthesis at the ribosome: kasugamycin, edeine, pactamycin, and GE81112.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.12
Figure 6.12

Antibiotics that block the phase of protein synthesis at the ribosome: erythromycin, GE2270A, tetracycline, streptomycin, kanamycin B, puromycin, and kirromycin.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.13
Figure 6.13

Many variants of the tetracycline scaffold have been used clinically, including minocycline, doxycycline, and tigecycline.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.14
Figure 6.14

(a) Tetracyclines (shown here is tigecycline in red) primarily bind to the A site of the 30S ribosomal subunit to block incoming aminoacyl-tRNAs. (Image created using PyMOL from PDB file 4V9B.) (b) Chelation of magnesium by tetracyclines is an important interaction in the noncovalent bonding network within the 70S ribosome.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.15
Figure 6.15

Aminoglycosides of clinical importance include gentamycin, tobramycin, and amikacin. The core 2-deoxystreptamine sugar is shown in red.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.16
Figure 6.16

(a) Binding of the aminoglycoside antibiotic neomycin (red) to the decoding site of the 30S ribosomal subunit while making critical interactions with bases in helix 69 of the 50S subunit. This mode of ribosome binding induces error-prone aminoacyl-tRNA accommodation. (Image created using PyMOL from PDB file 4V9C.) (b) The hydrogen bonding network for one of the neomycin binding sites interacting with helix 69 of the 50S ribosomal subunit is shown in blue, and helix 45 of the 30S subunit is shown in gray. At this site, neomycin interacts strongly with helix 69 bases and backbone phosphates while making a bridging interaction with a backbone phosphate of helix 45. This binding mode induces global conformational changes in the 70S ribosome (Wang et al., 2012).

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.17
Figure 6.17

Structures of synthetic oxazolidinone antibiotics. Linezolid is the first-generation compound, while torezolid and radezolid represent second-generation molecules. Torezolid was approved for use by the FDA on June 20, 2014.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.18
Figure 6.18

(a) Linezolid (red) binds to the PTC of the 50S ribosomal subunit and interacts with eight conserved RNA bases (according to the numbering system: U2585, A2451, C2452, U2506, G2505, U2504, A2503, and G2061). (b and c) The oxygen of the morpholine ring in linezolid forms a key hydrogen bond with N of U2585 (shown in pink), holding it in a catalytically unproductive conformation relative to U2585 (shown in blue) in the uninhibited wild-type (WT) 70S ribosome. (Images in panels a and b created using PyMOL from PDB file 3DLL [Wilson et al., 2008].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Vignette 6.1
Vignette 6.1

The second generation oxazolidinone antibiotic tedizolid is administered as a phosphate ester prodrug that gets cleaved by phosphatases for improved pharmacokinetics.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.19
Figure 6.19

Clarithromycin and telithromycin are second- and third-generation 14-membered macrolide antibiotics, with erythromycin being the first-generation and classic macrolide example.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.20
Figure 6.20

Tylosin and carbomycin are both macrolide antibiotics with a 16-membered macrocyclic core.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.21
Figure 6.21

(a) Schematic of carbomycin binding near the peptide exit tunnel (PET) of the 50S ribosomal subunit. (b) Binding of carbomycin (red) at the PTC, with the isobutyryl side chain (shown in blue) extending into the PTC. (Image created using PyMOL from PDB files 2WDK [30S subunit + tRNAs], 2WDL [50S subunit], 3J5L [ErmBL nascent peptide chain in PET shown in yellow], and 1K8A [carbomycin].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.22
Figure 6.22

(a) Erythromycin conformer at the PTC of the 50S ribosomal subunit. (Image created using PyMOL from PDB file 4V7U.) (b) Base-stacking interaction of the telithromycin heterobicyclic side chain with A752 and U2610 (indicated by blue double-headed arrows) and an additional hydrogen bond from telithromycin to A751 of the 50S subunit rRNA enhances binding affinity, resulting in increased antibiotic potency. (Image created using PyMOL from PDB file 4V7S.)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.23
Figure 6.23

Dalfopristin (a) and quinupristin (b), also known as streptogramins A and B, are the two components of the fixed-combination Synercid antibiotic. Important hydrogen bonds with 50S RNA bases are indicated with red dashed lines. (c) First, dalfopristin (red) binds in the 50S PTC, causing conformational changes in A2062 (native conformation is indicated by A2062-WT) and U2585 (native conformation is indicated by U2585-WT) that make peptide bond formation unfavorable and set the stage for quinupristin binding. (d) Quinupristin (green) binds at the end of the peptide exit tunnel, making key hydrogen bonds with the now distorted A2062 base pair. Ordered binding of the Synercid pair in the 50S subunit PTC gives rise to synergistic antibacterial activity. All numbering is based on the 70S ribosome. (Images in panels C and D generated using PyMOL from PDB file 1SM1 [Harms et al., 2004].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.24
Figure 6.24

Pleuromutilin, tiamulin, and retapamulin represent a new structural class of antibiotics approved by the FDA for human use.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.25
Figure 6.25

(a) A view of RNA bases in the 50S ribosomal subunit PTC with bound retapamulin (red) spanning the A and P tRNA sites. (Image created using PyMOL from PDB file 2OGO [Davidovich et al., 2007].) (b) Important hydrogen bonds are made between 50S RNA bases, while the tricyclic terpenoid scaffold is sandwiched between nucleotides. Base pair numbering is from the 70S ribosome.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.26
Figure 6.26

Clindamycin is a semisynthetic derivative (chlorine replacing hydroxyl) of the natural product antibiotic lincomycin, produced by , that binds to the PTC of the 50S ribosomal subunit.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.27
Figure 6.27

(a) Clindamycin (red) interacts with a large number of nucleotides at the PTC of the 50S ribosomal subunit. (Image created using PyMOL from PDB file 4V7V [Dunkle et al., 2007].) (b) Clindamycin forms an intricate hydrogen bonding network with PTC side chains including A2058, which can be methylated to confer clindamycin resistance. Base pair numbering is from the 70S ribosome.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.28
Figure 6.28

Structures of capreomycin and viomycin, nonribosomal peptide antibiotics from that span the 30S-50S ribosomal interface.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.29
Figure 6.29

(a) A view of the 70S ribosome with tRNAs and viomycin (red spheres) bound at the interface of the 30S and 50S subunits. (b) A closer view at the 30S-50S interface near the A-site tRNA, where viomycin sits. (c) The macrocyclic viomycin nonribosomal peptide core adopts a conformation favorable for this unique binding site, and the nonproteinogenic amino acids, especially the unusual β-ureidodehydroalanine, make important hydrogen bonds with nucleotide phosphate backbones. Base pair numbering is from the 70S ribosome. (PyMOL image created from PDB file 4V7L [Stanley et al., 2010].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.30
Figure 6.30

Structures of some thiazolyl peptide antibiotics: micrococcin P1, nosiheptide, thiostrepton, thiocillin II, GE2270A, and berninamycin. Most thiazolyl peptides have a central pyridine ring fused to a macrocyclic framework with a large amount of structural diversity dispersed throughout the rest of the scaffold. As seen for the bottom row of structures, the size of the macrocycle is variable, which has consequences for what biological target the molecule will favor.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.31
Figure 6.31

(a) The ribosomal binding site for nosiheptide (Nos) is between helix 43 (H43) of the 23S rRNA and a proline-rich region of L11 in the 50S ribosomal subunit. (b and c) Close-up views of the nosiheptide binding pocket interacting with RNA and polypeptide structural features of the ribosome. The thiazolyl peptides represent a rare example of ribosome inhibitors exploiting the RNA and polypeptide structural features of the ribosome. (Images created using PyMOL from PDB file 2ZJP.)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.32
Figure 6.32

(a) Chemical structure of everninomicin, a novel polysaccharide ribosome inhibitor. (b) While no crystal structure is available, the binding site has been mapped to interface with H43 and H44 helices of the 23S subunit, which perturbs binding of IF2. The binding site and mechanism of action are unique compared with other molecules discussed in this chapter. The image in panel b is identical to Fig. 6.8a except that all of the antibiotics are colored blue and the proposed everninomicin binding site is highlighted in red based on the residues that have been experimentally mapped (protein L16: R51, I52, R56; helix H89: G2482, G2470, C2471, C2480; helix H91: A2534, G2535 [Wilson, 2009]).

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.33
Figure 6.33

(a) The binding site of GE2270A overlaps with the 3′ end of Phe-aminoacyl-tRNA on EF-Tu. (b) A close-up view of the GE2270A–EF-Tu complex highlighted the distinct overlap with the Phe-tRNA. (Images created using PyMOL from aligned PDB files 2C77 [GE2270A–EF-Tu complex; Parmeggiani et al., 2006] and 1TTT [EF-Tu–Phe-tRNA complex; Nissen et al., 1995].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.34
Figure 6.34

Conversion of GE2270A to the more water-soluble clinical candidate LFF571 offers a promising route to commercializing this important class of ribosome-binding antibiotics. Novartis conducted a phase 2 trial with LFF571 for treatment of infections (LaMarche et al., 2012).

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Figure 6.35
Figure 6.35

(a) Comparison of GE2270A, kirromycin, and pulvomycin chemical structures. The molecules are inhibitors of the conditional GTPase EF-Tu but share no clear structural similarity. (b) The binding sites of these antibiotics are distinct but partially overlapping. The stick structures in the PyMOL image are color coded to match the chemical structures shown in panel a. (Three-dimensional image created by aligning PDB files 2C77 [GE2270A–EF-Tu complex], 1OB2 [kirromycin–EF-Tu complex], and 2C78 [pulvomycin–EF-Tu complex].)

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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Image of Vignette 6.2
Vignette 6.2

The anticonvulsant drug lamotrigine may serve as a lead scaffold to block assembly of bacterial 30S and 50S subunits into a functioning ribosome.

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6
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References

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Tables

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Table 6.1

Mechanisms of action, abbreviations, and PDB accession codes for a variety of antibiotics targeting the ribosome

Citation: Walsh C, Wencewicz T. 2016. Antibiotics That Block Protein Synthesis, p 114-146. In Antibiotics: Challenges, Mechanisms, Opportunities. ASM Press, Washington, DC. doi: 10.1128/9781555819316.ch6

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