PDBsum entry 4b3t

Ribosome

PDB id: 4b3t

Contents

Protein chains

235 a.a.

207 a.a.

208 a.a.

151 a.a.

101 a.a.

155 a.a.

138 a.a.

127 a.a.

99 a.a.

119 a.a.

125 a.a.

125 a.a.

60 a.a.

88 a.a.

84 a.a.

104 a.a.

73 a.a.

81 a.a.

99 a.a.

25 a.a.

DNA/RNA

Ligands

3TS

Metals

_MG ×219

__K ×17

_ZN ×2

Waters ×1

PDB id:

4b3t

Name:

Ribosome

Title:

Crystal structure of the 30s ribosome in complex with compound 39

Structure:

16s ribosomal RNA. Chain: a. 30s ribosomal protein s2. Chain: b. 30s ribosomal protein s3. Chain: c. 30s ribosomal protein s4. Chain: d. 30s ribosomal protein s5.

Source:

Thermus thermophilus hb8. Organism_taxid: 300852. Organism_taxid: 300852

Resolution:

3.00Å R-factor: 0.210 R-free: 0.243

Authors:

C.L.Ng,K.Lang,D.Shcherbakov,T.Matt,D.Perez-Fernandez,R.Patak,M.Meyer, S.Duscha,R.Akbergenov,H.Boukari,P.Freihofer,I.Kudyba,M.S.K.Reddy, R.S.Nandurikar,V.Ramakrishnan,A.Vasella,E.C.Bottger

Key ref:

D.Perez-Fernandez et al. (2014). 4'-O-substitutions determine selectivity of aminoglycoside antibiotics. Nat Commun, 5, 3112. PubMed id: 24473108 DOI: 10.1038/ncomms4112

Date:

26-Jul-12 Release date: 07-Aug-13

Protein chain

P80371  (RS2_THET8) -  Small ribosomal subunit protein uS2 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 256 a.a.

Struc: 235 a.a.

Protein chain

P80372  (RS3_THET8) -  Small ribosomal subunit protein uS3 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 239 a.a.

Struc: 207 a.a.

Protein chain

P80373  (RS4_THET8) -  Small ribosomal subunit protein uS4 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 209 a.a.

Struc: 208 a.a.

Protein chain

Q5SHQ5  (RS5_THET8) -  Small ribosomal subunit protein uS5 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 162 a.a.

Struc: 151 a.a.

Protein chain

Q5SLP8  (RS6_THET8) -  Small ribosomal subunit protein bS6 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 101 a.a.

Struc: 101 a.a.

Protein chain

P17291  (RS7_THET8) -  Small ribosomal subunit protein uS7 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 156 a.a.

Struc: 155 a.a.

Protein chain

P0DOY9  (RS8_THET8) -  Small ribosomal subunit protein uS8 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 138 a.a.

Struc: 138 a.a.

Protein chain

P80374  (RS9_THET8) -  Small ribosomal subunit protein uS9 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 128 a.a.

Struc: 127 a.a.*

Protein chain

Q5SHN7  (RS10_THET8) -  Small ribosomal subunit protein uS10 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 105 a.a.

Struc: 99 a.a.

Protein chain

P80376  (RS11_THET8) -  Small ribosomal subunit protein uS11 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 129 a.a.

Struc: 119 a.a.

Protein chain

Q5SHN3  (RS12_THET8) -  Small ribosomal subunit protein uS12 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 132 a.a.

Struc: 125 a.a.

Protein chain

P80377  (RS13_THET8) -  Small ribosomal subunit protein uS13 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 126 a.a.

Struc: 125 a.a.

Protein chain

P0DOY6  (RS14Z_THET8) -  Small ribosomal subunit protein uS14 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 61 a.a.

Struc: 60 a.a.

Protein chain

Q5SJ76  (RS15_THET8) -  Small ribosomal subunit protein uS15 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 89 a.a.

Struc: 88 a.a.

Protein chain

Q5SJH3  (RS16_THET8) -  Small ribosomal subunit protein bS16 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 88 a.a.

Struc: 84 a.a.

Protein chain

P0DOY7  (RS17_THET8) -  Small ribosomal subunit protein uS17 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 105 a.a.

Struc: 104 a.a.*

Protein chain

Q5SLQ0  (RS18_THET8) -  Small ribosomal subunit protein bS18 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 88 a.a.

Struc: 73 a.a.*

Protein chain

Q5SHP2  (RS19_THET8) -  Small ribosomal subunit protein uS19 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 93 a.a.

Struc: 81 a.a.

Protein chain

P80380  (RS20_THET8) -  Small ribosomal subunit protein bS20 from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 106 a.a.

Struc: 99 a.a.*

Protein chain

Q5SIH3  (RSHX_THET8) -  Small ribosomal subunit protein bTHX from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 27 a.a.

Struc: 25 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DNA/RNA chains

U-G-G-A-G-A-G-U-U-U-G-A-U-C-C-U-G-G-C-U-C-A-G-G-G-U-G-A-A-C-G-C-U-G-G-C-G-G-C- ... 1512 bases

U-U-C-A 4 bases

G-G-G-A-U-U-G-A-A-A-A-U-C-C-C 15 bases

DOI no: 10.1038/ncomms4112

Nat Commun 5:3112 (2014)

PubMed id: 24473108

4'-O-substitutions determine selectivity of aminoglycoside antibiotics.

D.Perez-Fernandez, D.Shcherbakov, T.Matt, N.C.Leong, I.Kudyba, S.Duscha, H.Boukari, R.Patak, S.R.Dubbaka, K.Lang, M.Meyer, R.Akbergenov, P.Freihofer, S.Vaddi, P.Thommes, V.Ramakrishnan, A.Vasella, E.C.Böttger.

ABSTRACT

Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.