Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
Abstract
:1. Introduction
2. X-ray Structure Characterization of Macrolide-Ribosome Complexes
3. Cryo-EM Imaging of Macrolide-Targeted Ribosomes
4. Probing Macrolide Interactions by NMR Spectroscopy
5. Other Methods for Macrolide Binding Studies
6. Computational Simulations of Macrolide Interactions
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PTC | peptidyl transferase center |
FDA | U.S. Food and Drug Administration |
cryo-EM | cryogenic electron microscopy |
NMR | nuclear magnetic resonance |
rf | radiofrequency |
FID | free induction decay |
FT | Fourier transformation |
MD | molecular dynamics |
NPET | nascent peptide exit tunnel |
MABP-1 | macrolide antibiotic binding protein-1 |
SEM | scanning electron microscopy |
SPA | single-particle analysis |
cryo-ET | cryogenic electron tomography |
ErmBL | erythromycin resistance methyltransferase B leader peptide |
ErmCL | erythromycin resistance methyltransferase C leader peptide |
ermaa-tRNA | erythromycin resistance methyltransferase geneaminoacyl-tRNA |
p-tRNA | peptidyl-tRNA |
TnaCMsrE | tryptophanase leader peptide |
RSF | macrolide-streptogramin B resistance proteinribosomal silencing factor |
ABC | ATP-binding cassette |
NOE | nuclear Overhauser effect |
STD | saturation transfer difference |
trNOESY | transferred nuclear Overhauser effect spectroscopy |
DOSY | diffusion-ordered NMR spectroscopy |
PREs | paramagnetic relaxation enhancements |
ROESY | rotating frame nuclear Overhauser effect spectroscopy |
SDS | sodium dodecylsulphate |
DPC | dodecylphosphocholine |
BSA | bovine serum albumin |
MRSA | methicillin-resistant Staphylococcus aureus |
MAS | magic angle spinning |
DOPC | dioleoylphosphatidylcholine |
ESR | electron spin resonance |
DMPC | 1,2-dimyristoyl-sn-glycero-3-phosphocholine |
DMPG | 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol |
SAR | structure-activity relationship |
RDC | residual dipolar couplings |
DMS | dimethyl sulfate |
CMCT | 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate |
F | fluorophore |
FRET | Förster resonance energy transfer |
QM | quantum mechanical |
AMBER | Assisted Model Building and Energy Refinement |
pBLCLZα | erythromycin-inducible ermC-β-galactosidase |
CHARMM | Chemistry at HARvard Macromolecular Mechanics |
PES | potential energy surface |
ffTK | force field toolkit |
VMD | variable molecular dynamics |
GCMC | grand canonical Monte Carlo |
MMFF | Merck Molecular Force Field |
MOE | MOELowModeMD |
MC | MacroModel |
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Compound | Code | Resolution/Å | Distance/Å | |||||
---|---|---|---|---|---|---|---|---|
C3–C11 | C4–C11 | C4–C6Me | C5–C6Me | C3–C8 | C8–C11 | |||
Erythromycin, folded out 1 | NAVTAF | 0.85 | 4.69 | 4.33 | 3.90 | 2.52 | 5.50 | 3.65 |
Azithromycin, folded out 1 | GEGJAD | 0.82 | 4.86 | 4.60 | 3.92 | 2.50 | 5.74 | 4.80 |
Erythromycin bound to the H. marismortui 50S subunit [11] 2 | 1YI2 | 2.65 | 4.85 | 4.55 | 3.99 | 2.61 | 5.64 | 3.59 |
Azithromycin bound to the H. marismortui 50S subunit [11] 2 | 1YHQ | 2.40 | 4.80 | 5.01 | 4.03 | 2.59 | 5.76 | 4.62 |
Azithromycin bound to the H. marismortui 50S subunit [27] 2 | 1M1K | 3.20 | 5.00 | 4.74 | 3.92 | 2.55 | 5.82 | 4.84 |
Erythromycin bound to the T. thermpohilus ribosome [28] 2 | 4V7X | 3.00 | 4.85 | 4.55 | 3.99 | 2.61 | 5.64 | 3.59 |
Azithromycin bound to the T. thermpohilus ribosome [28] 2 | 4V7Y | 3.00 | 4.80 | 5.01 | 4.03 | 2.59 | 5.76 | 4.62 |
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Jednačak, T.; Mikulandra, I.; Novak, P. Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics. Int. J. Mol. Sci. 2020, 21, 7799. https://doi.org/10.3390/ijms21207799
Jednačak T, Mikulandra I, Novak P. Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics. International Journal of Molecular Sciences. 2020; 21(20):7799. https://doi.org/10.3390/ijms21207799
Chicago/Turabian StyleJednačak, Tomislav, Ivana Mikulandra, and Predrag Novak. 2020. "Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics" International Journal of Molecular Sciences 21, no. 20: 7799. https://doi.org/10.3390/ijms21207799