1J1A

PANCREATIC SECRETORY PHOSPHOLIPASE A2 (IIa) WITH ANTI-INFLAMMATORY ACTIVITY

Summary for 1J1A

• Entry DOI: 10.2210/pdb1j1a/pdb
• Descriptor: Phospholipase A2, CALCIUM ION, (S)-5-(4-BENZYLOXY-PHENYL)-4-(7-PHENYL-HEPTANOYLAMINO)-PENTANOIC ACID, ... (4 entities in total)
• Functional Keywords: medicinal chemistry, enzyme inhibitor, structure-activity relationships, inflammation, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Peripheral membrane protein: P14555
• Total number of polymer chains: 2
• Total formula weight: 29025.60

Authors

Hansford, K.A.,Reid, R.C.,Clark, C.I.,Tyndall, J.D.A.,Whitehouse, M.W.,Guthrie, T.,McGeary, R.P.,Schafer, K.,Martin, J.L.,Fairlie, D.P. (deposition date: 2002-12-03, release date: 2003-03-18, Last modification date: 2024-11-13)

Primary citation

Hansford, K.A.,Reid, R.C.,Clark, C.I.,Tyndall, J.D.A.,Whitehouse, M.W.,Guthrie, T.,McGeary, R.P.,Schafer, K.,Martin, J.L.,Fairlie, D.P.
D-Tyrosine as a Chiral Precusor to Potent Inhibitors of Human Nonpancreatic Secretory Phospholipase A2 (IIa) with Antiinflammatory Activity
Chembiochem, 4:181-185, 2003

PubMed Abstract: Few reported inhibitors of secretory phospholipase A(2) enzymes truly inhibit the IIa human isoform (hnpsPLA(2)-IIa) noncovalently at submicromolar concentrations. Herein, the simple chiral precursor D-tyrosine was derivatised to give a series of potent new inhibitors of hnpsPLA(2)-IIa. A 2.2-A crystal structure shows an inhibitor bound in the active site of the enzyme, chelated to a Ca(2+) ion through carboxylate and amide oxygen atoms, H-bonded through an amide NH group to His48, with multiple hydrophobic contacts and a T-shaped aromatic-group-His6 interaction. Antiinflammatory activity is also demonstrated for two compounds administered orally to rats.

PubMed: 12616631
DOI: 10.1002/cbic.200390029

Experimental method

X-RAY DIFFRACTION (2.2 Å)