PDBsum entry: 1k8a

Ribosome

PDB id: 1k8a

Contents

Protein chains

237 a.a. *

337 a.a. *

246 a.a. *

140 a.a. *

172 a.a. *

119 a.a. *

29 a.a. *

156 a.a. *

142 a.a. *

132 a.a. *

145 a.a. *

194 a.a. *

186 a.a. *

115 a.a. *

143 a.a. *

95 a.a. *

150 a.a. *

81 a.a. *

119 a.a. *

53 a.a. *

65 a.a. *

154 a.a. *

82 a.a. *

142 a.a. *

73 a.a. *

56 a.a. *

46 a.a. *

92 a.a. *

DNA/RNA

Ligands

CAI

Metals

__K ×3

_NA ×83

_CL ×23

_MG ×119

_CD ×5

Waters ×7850

* Residue conservation analysis

PDB id:

1k8a

Name:

Ribosome

Title:

Co-crystal structure of carbomycin a bound to the 50s ribosomal subunit of haloarcula marismortui

Structure:

23s rrna. Chain: a. 5s rrna. Chain: b. Ribosomal protein l2. Chain: c. Synonym: 50s ribosomal protein l2p, hmal2, hl4. Ribosomal protein l3. Chain: d.

Source:

Haloarcula marismortui. Organism_taxid: 2238. Organism_taxid: 2238

Resolution:

3.00Å R-factor: 0.227 R-free: 0.265

Authors:

J.L.Hansen,J.A.Ippolito,N.Ban,P.Nissen,P.B.Moore,T.Steitz

Key ref:

J.L.Hansen et al. (2002). The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell, 10, 117-128. PubMed id: 12150912 DOI: 10.1016/S1097-2765(02)00570-1

Date:

23-Oct-01 Release date: 19-Jul-02

Protein chain

P20276  (RL2_HALMA) -  50S ribosomal protein L2P

Seq: 240 a.a.

Struc: 237 a.a.*

Protein chain

P20279  (RL3_HALMA) -  50S ribosomal protein L3P

Seq: 338 a.a.

Struc: 337 a.a.

Protein chain

P12735  (RL4_HALMA) -  50S ribosomal protein L4P

Seq: 246 a.a.

Struc: 246 a.a.*

Protein chain

P14124  (RL5_HALMA) -  50S ribosomal protein L5P

Seq: 177 a.a.

Struc: 140 a.a.

Protein chain

P14135  (RL6_HALMA) -  50S ribosomal protein L6P

Seq: 178 a.a.

Struc: 172 a.a.

Protein chain

P12743  (RL7A_HALMA) -  50S ribosomal protein L7Ae

Seq: 120 a.a.

Struc: 119 a.a.*

Protein chain

P15825  (RLA0_HALMA) -  50S ribosomal protein L10E

Seq: 348 a.a.

Struc: 29 a.a.*

Protein chain

P60617  (RL10_HALMA) -  50S ribosomal protein L10e

Seq: 177 a.a.

Struc: 156 a.a.*

Protein chain

P29198  (RL13_HALMA) -  50S ribosomal protein L13P

Seq: 145 a.a.

Struc: 142 a.a.

Protein chain

P22450  (RL14_HALMA) -  50S ribosomal protein L14P

Seq: 132 a.a.

Struc: 132 a.a.

Protein chain

P12737  (RL15_HALMA) -  50S ribosomal protein L15P

Seq: 165 a.a.

Struc: 145 a.a.

Protein chain

P60618  (RL15E_HALMA) -  50S ribosomal protein L15e

Seq: 196 a.a.

Struc: 194 a.a.*

Protein chain

P14123  (RL18_HALMA) -  50S ribosomal protein L18P

Seq: 187 a.a.

Struc: 186 a.a.

Protein chain

P12733  (RL18E_HALMA) -  50S ribosomal protein L18e

Seq: 116 a.a.

Struc: 115 a.a.

Protein chain

P14119  (RL19_HALMA) -  50S ribosomal protein L19e

Seq: 149 a.a.

Struc: 143 a.a.*

Protein chain

P12734  (RL21_HALMA) -  50S ribosomal protein L21e

Seq: 96 a.a.

Struc: 95 a.a.

Protein chain

P10970  (RL22_HALMA) -  50S ribosomal protein L22P

Seq: 155 a.a.

Struc: 150 a.a.

Protein chain

P12732  (RL23_HALMA) -  50S ribosomal protein L23P

Seq: 85 a.a.

Struc: 81 a.a.

Protein chain

P10972  (RL24_HALMA) -  50S ribosomal protein L24P

Seq: 120 a.a.

Struc: 119 a.a.

Protein chain

P14116  (RL24E_HALMA) -  50S ribosomal protein L24e

Seq: 67 a.a.

Struc: 53 a.a.

Protein chain

P10971  (RL29_HALMA) -  50S ribosomal protein L29P

Seq: 71 a.a.

Struc: 65 a.a.

Protein chain

P14121  (RL30_HALMA) -  50S ribosomal protein L30P

Seq: 154 a.a.

Struc: 154 a.a.

Protein chain

P18138  (RL31_HALMA) -  50S ribosomal protein L31e

Seq: 92 a.a.

Struc: 82 a.a.

Protein chain

P12736  (RL32_HALMA) -  50S ribosomal protein L32e

Seq: 241 a.a.

Struc: 142 a.a.

Protein chain

P60619  (RL37A_HALMA) -  50S ribosomal protein L37Ae

Seq: 92 a.a.

Struc: 73 a.a.*

Protein chain

P32410  (RL37_HALMA) -  50S ribosomal protein L37e

Seq: 57 a.a.

Struc: 56 a.a.

Protein chain

P22452  (RL39_HALMA) -  50S ribosomal protein L39e

Seq: 50 a.a.

Struc: 46 a.a.*

Protein chain

P32411  (RL44_HALMA) -  50S ribosomal protein L44E

Seq: 92 a.a.

Struc: 92 a.a.

* PDB and UniProt seqs differ at 185 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (4 terms)
• Biological process: ribosome biogenesis (3 terms)
• Biochemical function: structural constituent of ribosome (9 terms)

DOI no: 10.1016/S1097-2765(02)00570-1

Mol Cell 10:117-128 (2002)

PubMed id: 12150912

The structures of four macrolide antibiotics bound to the large ribosomal subunit.

J.L.Hansen, J.A.Ippolito, N.Ban, P.Nissen, P.B.Moore, T.A.Steitz.

ABSTRACT

Crystal structures of the Haloarcula marismortui large ribosomal subunit complexed with the 16-membered macrolide antibiotics carbomycin A, spiramycin, and tylosin and a 15-membered macrolide, azithromycin, show that they bind in the polypeptide exit tunnel adjacent to the peptidyl transferase center. Their location suggests that they inhibit protein synthesis by blocking the egress of nascent polypeptides. The saccharide branch attached to C5 of the lactone rings extends toward the peptidyl transferase center, and the isobutyrate extension of the carbomycin A disaccharide overlaps the A-site. Unexpectedly, a reversible covalent bond forms between the ethylaldehyde substituent at the C6 position of the 16-membered macrolides and the N6 of A2103 (A2062, E. coli). Mutations in 23S rRNA that result in clinical resistance render the binding site less complementary to macrolides.

Selected figure(s)

Figure 1.
Figure 1. Chemical Structures of the Macrolides, Tylosin, Carbomycin A, Spiramycin, Azithromycin, and ErythromycinAtoms in these figures and in the Protein Data Bank coordinate files (1K8A, 1K9M, 1M1K, and 1KD1) are named according to Paesen et al. (1995), with the numbering of the atoms of the lactone ring starting at the ester bond. Oxygen atoms are numbered according to the adjacent carbon atoms, and sugar atom numbers are modified by suffixes A, B, or C to distinguish mycaminose, mycarose, and any additional sugar, respectively.

Figure 5.
Figure 5. Comparison of the Interactions of Different Macrolides with the Ribosome(A) Carbomycin (red), tylosin (orange), spiramycin (yellow), and azithromycin (blue) bind the ribosome in an almost identical fashion and cover G2099 (A2058) and A2100 (2059) (green spheres). The lactone ring is extended further into the tunnel by mycinose on tylosin and forosamine on spiramycin. The disaccharide moiety extends the 16-membered macrolides in the opposite direction toward the catalytic center. Upon 16-membered macrolide binding (but not azithromycin), the base of A2103 (2062) (dark green) moves (curved white line) from its location against the wall of the exit tunnel to an extended conformation (light green sticks) and forms a covalent bond with the macrolide (orange sticks). The isobutyrate group of carbomycin A (red) reaches into the tRNA A-site (dark blue and purple spheres). The mycinose moiety of tylosin (orange) contacts protein L22. The forosamine moiety of spiramycin (yellow) contacts L4. The cladinose sugar of azithromycin binds in a fourth sugar binding pocket. These three macrolides were aligned by least squares superimposition of the phosphates of ribosomal RNA.(B) Alignment of erythromycin (white) bound to the D. radiodurans large subunit (Schlünzen et al., 2001) with azithromycin (blue) bound to the H. marismortui large subunit.

The above figures are reprinted by permission from Cell Press: Mol Cell (2002, 10, 117-128) copyright 2002.

Figures were selected by the author.