1j1a: Difference between revisions
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|PDB= 1j1a |SIZE=350|CAPTION= <scene name='initialview01'>1j1a</scene>, resolution 2.20Å | |PDB= 1j1a |SIZE=350|CAPTION= <scene name='initialview01'>1j1a</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=BHP:(S)-5-(4-BENZYLOXY-PHENYL)-4-(7-PHENYL-HEPTANOYLAMINO)-PENTANOIC+ACID'>BHP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j1a OCA], [http://www.ebi.ac.uk/pdbsum/1j1a PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1j1a RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Tyndall, J D.A.]] | [[Category: Tyndall, J D.A.]] | ||
[[Category: Whitehouse, M W.]] | [[Category: Whitehouse, M W.]] | ||
[[Category: enzyme inhibitor]] | [[Category: enzyme inhibitor]] | ||
[[Category: inflammation]] | [[Category: inflammation]] | ||
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[[Category: structure-activity relationship]] | [[Category: structure-activity relationship]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:27:35 2008'' | ||
