User:Wayne Decatur/Haloarcula Large Ribosomal Subunit With Azithromycin

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Azithromycin is a 15-membered macrolide antibiotic of the azalide subclass. The structure of this clinically important antibiotic has been solved bound to the Haloarcula marismortui large ribosomal subunit revealing its mode of inhibiting protein synthesis[1][2].

The basic details of the Haloarcula marismortui large ribosomal subunit are described in its own entry while the structure of azithromycin (zithromax) and its interaction with the ribosome are shown below on this page.

Contents

Mechanism of action

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Azithromycin bound to the Large Ribosomal Subunit (1m1k), resolution 3.2Å ().
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Summary: Azithromycin, like other macrolides, binds in the polypeptide exit tunnel near its start the polypeptide exit tunnel inhibiting protein synthesis by blocking the progression of nascent polypeptides through the tunnel. The polypeptide exit tunnel is described here.

About this Structure

1m1k is a 30 chains structure of sequences from Haloarcula marismortui. Full crystallographic information is available from OCA. A version of 1m1k optimized for use online as described here is used on this page. You may wish to examine the basics of the subunit.

Reference for the Structure

  • Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell. 2002 Jul;10(1):117-28. PMID:12150912

Related Structures

  • Haloarcula Large Ribosomal Subunit
  • Interactions between Antibiotics and the Ribosome
  • 1nwy The Large Ribosomal Subunit From Deinococcus radiodurans complexed with Azithromycin[3]
  • 1yhq Haloarcula marismortui large ribosomal subunit containing the mutation G2099A (A2058 in E. coli) complexed with Azithromycin - despite the change to the eubacterial-like adenosine at this position azithromycin binds essentially the same way to either Haloarcula subunit[4]
  • 1kd1 The Large Ribosomal Subunit From H. marismortui complexed with the 16-membered macrolide spiramycin[5]
  • 1k9m The Large Ribosomal Subunit From H. marismortui complexed with the 16-membered macrolide Tylosin[6]
  • 1k8a The Large Ribosomal Subunit From H. marismortui complexed with the 16-membered macrolide Carbomycin A[7]
  • 3cc2 The refined structure of the Large Ribosomal Subunit From H. marismortui[8]

References

  1. ↑ Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell. 2002 Jul;10(1):117-28. PMID:12150912
  2. ↑ Tu D, Blaha G, Moore PB, Steitz TA. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell. 2005 Apr 22;121(2):257-70. PMID:15851032 doi:10.1016/j.cell.2005.02.005
  3. ↑ Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A. Structural basis for the antibiotic activity of ketolides and azalides. Structure. 2003 Mar;11(3):329-38. PMID:12623020
  4. ↑ Tu D, Blaha G, Moore PB, Steitz TA. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell. 2005 Apr 22;121(2):257-70. PMID:15851032 doi:10.1016/j.cell.2005.02.005
  5. ↑ Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell. 2002 Jul;10(1):117-28. PMID:12150912
  6. ↑ Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell. 2002 Jul;10(1):117-28. PMID:12150912
  7. ↑ Hansen JL, Ippolito JA, Ban N, Nissen P, Moore PB, Steitz TA. The structures of four macrolide antibiotics bound to the large ribosomal subunit. Mol Cell. 2002 Jul;10(1):117-28. PMID:12150912
  8. ↑ Blaha G, Gurel G, Schroeder SJ, Moore PB, Steitz TA. Mutations outside the anisomycin-binding site can make ribosomes drug-resistant. J Mol Biol. 2008 Jun 6;379(3):505-19. Epub 2008 Apr 8. PMID:18455733 doi:http://dx.doi.org/10.1016/j.jmb.2008.03.075

Additional Literature and Resources

  • Steitz TA. Structural insights into the functions of the large ribosomal subunit, a major antibiotic target. Keio J Med. 2008 Mar;57(1):1-14. PMID:18382121
  • Steitz TA. On the structural basis of peptide-bond formation and antibiotic resistance from atomic structures of the large ribosomal subunit. FEBS Lett. 2005 Feb 7;579(4):955-8. PMID:15680981 doi:10.1016/j.febslet.2004.11.053

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Wayne Decatur

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