Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.1.1.4 extracted from

  • Dalm, D.; Palm, G.J.; Aleksandrov, A.; Simonson, T.; Hinrichs, W.
    Nonantibiotic properties of tetracyclines: structural basis for inhibition of secretory phospholipase A2 (2010), J. Mol. Biol., 398, 83-96.
    View publication on PubMed

Application

Application Comment Organism
drug development applicability of minocycline as a lead compound for the design of specific inhibitors of PLA2, which play a crucial role in inflammatory processes Naja naja

Crystallization (Commentary)

Crystallization (Comment) Organism
PLA2 in complex with inhibitor minocycline, by hanging drop vapor diffusion method, at 1.65 A resolution. Belongs to space group P213 with unit cell parameters a = 68.712 A, b = 68.712 A, c = 68.712 A. Minocycline binds to the hydrophobic cleft at the entrance of the active site of PLA2. As a consequence, the access of substrate molecules to the active site is blocked, and the conformation of the Ca2+-binding loop is stabilized in the Ca2+-free conformation of the apo-enzyme, thus resulting in inhibition of enzymatic activity. Interaction between PLA2 and minocycline is mainly hydrophobic Naja naja

Inhibitors

Inhibitors Comment Organism Structure
minocycline 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. Dissociation constant for PLA2 is Kd = 0.00018 M Naja naja

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ Ca2+ is coordinated by the Asp48 carboxylate, two water molecules, and three polypeptide carbonyl oxygen atoms of the Ca2+-binding loop Naja naja

Organism

Organism UniProt Comment Textmining
Naja naja P15445
-
-

Purification (Commentary)

Purification (Comment) Organism
by centrifugation and on anion-exchange column Naja naja

Source Tissue

Source Tissue Comment Organism Textmining
venom
-
Naja naja
-

Subunits

Subunits Comment Organism
trimer crystallography Naja naja

Synonyms

Synonyms Comment Organism
PLA2
-
Naja naja
secretory phospholipase A2
-
Naja naja