Nonantibiotic properties of tetracyclines: Structural basis for inhibition of secretory phospholipase A2

Daniela Dalm, Gottfried J. Palm, Alexey Aleksandrov, Thomas Simonson, Winfried Hinrichs

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Secretory phospholipase A2 is involved in inflammatory processes and was previously shown to be inhibited by lipophilic tetracyclines such as minocycline (minoTc) and doxycycline. Lipophilic tetracyclines might be a new lead compound for the design of specific inhibitors of secretory phospholipase A2, which play a crucial role in inflammatory processes. Our X-ray crystal structure analysis at 1.65 Å resolution of the minoTc complex of phospholipase A2 (PLA2) of the Indian cobra (Naja naja naja) is the first example of nonantibiotic tetracycline interactions with a protein. MinoTc interferes with the conformation of the active-site Ca2+-binding loop, preventing Ca2+ binding, and shields the active site from substrate entrance, resulting in inhibition of the enzyme. MinoTc binding to PLA2 is dominated by hydrophobic interactions quite different from antibiotic recognition of tetracyclines by proteins or the ribosome. The affinity of minoTc for PLA2 was determined by surface plasmon resonance, resulting in a dissociation constant Kd=1.8×10-4 M.

Original languageEnglish (US)
Pages (from-to)83-96
Number of pages14
JournalJournal of Molecular Biology
Issue number1
StatePublished - Apr 2010
Externally publishedYes


  • Anti-inflammatory
  • Minocycline
  • Nonantibiotic
  • Phospholipase
  • X-ray crystallography

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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