1j1a

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Revision as of 15:29, 12 November 2007

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spinqualitylabelsall models 1j1a, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[172411]

About this Structure

1J1A is a Single protein structure of sequence from Homo sapiens with CA and BHP as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.

Reference

D-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A2 (IIa) with antiinflammatory activity., Hansford KA, Reid RC, Clark CI, Tyndall JD, Whitehouse MW, Guthrie T, McGeary RP, Schafer K, Martin JL, Fairlie DP, Chembiochem. 2003 Mar 3;4(2-3):181-5. PMID:12616631

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