2WQ5: Non-antibiotic Properties Of Tetracyclines: Structural Basis For Inhibition Of Secretory Phospholipase A2

Citation:
Abstract
Secretory phospholipase A(2) 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 A(2), which play a crucial role in inflammatory processes. Our X-ray crystal structure analysis at 1.65 A resolution of the minoTc complex of phospholipase A(2) (PLA(2)) 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 Ca(2+)-binding loop, preventing Ca(2)(+) binding, and shields the active site from substrate entrance, resulting in inhibition of the enzyme. MinoTc binding to PLA(2) is dominated by hydrophobic interactions quite different from antibiotic recognition of tetracyclines by proteins or the ribosome. The affinity of minoTc for PLA(2) was determined by surface plasmon resonance, resulting in a dissociation constant K(d)=1.8 x 10(-)(4) M.
PDB ID: 2WQ5Download
MMDB ID: 80905
PDB Deposition Date: 2009/8/13
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 1.65  Å
Source Organism:
Similar Structures:
Biological Unit for 2WQ5: trimeric; determined by author and by software (PISA)
Molecular Components in 2WQ5
Label Count Molecule
Proteins (3 molecules)
3
Phospholipase A2, Acidic
Molecule annotation
Chemicals (9 molecules)
1
3
2
3
3
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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