9PII image
Deposition Date 2025-07-10
Release Date 2026-05-13
Last Version Date 2026-09-23
Entry Detail
PDB ID:
9PII
Keywords:
Title:
E. coli 70S ribosome bound to Sarecycline
Biological Source:
Source Organism(s):
Escherichia coli (Taxon ID: 562)
Method Details:
Experimental Method:
Resolution:
2.40 Å
Aggregation State:
PARTICLE
Reconstruction Method:
SINGLE PARTICLE
Macromolecular Entities
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L33
Gene (Uniprot):rpmG
Chain IDs:A (auth: 0)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L34
Gene (Uniprot):rpmH
Chain IDs:B (auth: 1)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L35
Gene (Uniprot):rpmI
Chain IDs:C (auth: 2)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L36
Gene (Uniprot):rpmJ
Chain IDs:D (auth: 3)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L31
Gene (Uniprot):rpmE
Chain IDs:E (auth: 4)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polyribonucleotide
Molecule:16S rRNA
Chain IDs:F (auth: A)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:30S ribosomal protein S2
Gene (Uniprot):rpsB
Chain IDs:G (auth: B)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsC
Chain IDs:H (auth: C)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsD
Chain IDs:I (auth: D)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsE
Chain IDs:J (auth: E)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsF
Chain IDs:K (auth: F)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsG
Chain IDs:L (auth: G)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsH
Chain IDs:M (auth: H)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsI
Chain IDs:N (auth: I)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsJ
Chain IDs:O (auth: J)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:30S ribosomal protein S11
Gene (Uniprot):rpsK
Chain IDs:P (auth: K)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsL
Chain IDs:Q (auth: L)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsM
Chain IDs:R (auth: M)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsN
Chain IDs:S (auth: N)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsO
Chain IDs:T (auth: O)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsP
Chain IDs:U (auth: P)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsQ
Chain IDs:V (auth: Q)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsR
Chain IDs:W (auth: R)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsS
Chain IDs:X (auth: S)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsT
Chain IDs:Y (auth: T)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Small ribosomal subunit prote
Gene (Uniprot):rpsU
Chain IDs:Z (auth: U)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polyribonucleotide
Molecule:mRNA
Chain IDs:AA (auth: X)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polyribonucleotide
Molecule:P-site tRNA
Chain IDs:BA (auth: Z)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polyribonucleotide
Molecule:23S rRNA
Chain IDs:CA (auth: a)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polyribonucleotide
Molecule:5S rRNA
Chain IDs:DA (auth: b)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L2
Gene (Uniprot):rplB
Chain IDs:EA (auth: c)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L3
Gene (Uniprot):rplC
Chain IDs:FA (auth: d)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplD
Chain IDs:GA (auth: e)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplE
Chain IDs:HA (auth: f)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplF
Chain IDs:IA (auth: g)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplI
Chain IDs:JA (auth: h)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplM
Chain IDs:KA (auth: i)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplN
Chain IDs:LA (auth: j)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplO
Chain IDs:MA (auth: k)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L16
Gene (Uniprot):rplP
Chain IDs:NA (auth: l)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplQ
Chain IDs:OA (auth: m)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplR
Chain IDs:PA (auth: n)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplS
Chain IDs:QA (auth: o)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L20
Gene (Uniprot):rplT
Chain IDs:RA (auth: p)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Ribosomal protein L21
Gene (Uniprot):rplU
Chain IDs:SA (auth: q)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L22
Gene (Uniprot):rplV
Chain IDs:TA (auth: r)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L23
Gene (Uniprot):rplW
Chain IDs:UA (auth: s)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L24
Gene (Uniprot):rplX
Chain IDs:VA (auth: t)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rplY
Chain IDs:WA (auth: u)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L27
Gene (Uniprot):rpmA
Chain IDs:XA (auth: v)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L28
Gene (Uniprot):rpmB
Chain IDs:YA (auth: w)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:Large ribosomal subunit prote
Gene (Uniprot):rpmC
Chain IDs:ZA (auth: x)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L30
Gene (Uniprot):rpmD
Chain IDs:AB (auth: y)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Polymer Type:polypeptide(L)
Molecule:50S ribosomal protein L32
Gene (Uniprot):rpmF
Chain IDs:BB (auth: z)
Chain Length:0
Number of Molecules:1
Biological Source:Escherichia coli
Modified Residue
Compound ID Chain ID Parent Comp ID Details 2D Image
2MG F G modified residue
4D4 NA ARG modified residue
4OC F C modified residue
5MC F C modified residue
D2T Q ASP modified residue
G7M F G modified residue
MA6 F A modified residue
MEQ FA GLN modified residue
PSU F U modified residue
UR3 F U modified residue
Primary Citation
Dual site targeting of the bacterial 70S ribosome by tetracyclines.
Nat Commun 17 ? ? (2026)
PMID: 42156748 DOI: 10.1038/s41467-026-72788-9

Abstact

The tetracycline class of antibiotics is widely used for treating bacterial diseases including Lyme disease, anthrax, acne vulgaris, and pneumonia. Using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we show that tetracyclines can simultaneously target the mRNA decoding center in the 30S subunit and the nascent peptide exit tunnel (NPET) in the 50S subunit of the bacterial ribosome. Among the tested tetracyclines, Doxycycline was distinct in its ability to dimerize and bind the NPET at multiple locations. Structural comparison of Doxycycline, Minocycline, and Sarecycline bound to the Escherichia coli and Cutibacterium acnes 70S ribosome revealed species-specific differences affecting drug interaction and occupancy. Our results reveal a dual site mechanism of action for tetracyclines and provide a structural basis for rational design of narrow spectrum tetracyclines to overcome the rising threat of antibiotic resistance.

Legend

Protein

Chemical

Disease

Primary Citation of related structures
Feedback Form
Name
Email
Institute
Feedback