1j1a: Difference between revisions

Revision as of 20:40, 2 May 2008

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

OverviewOverview

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 StructureAbout this Structure

1J1A is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 20:40:41 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1j1a.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1j1a |SIZE=350|CAPTION= <scene name='initialview01'>1j1a</scene>, resolution 2.20&Aring;
+The line below this paragraph, containing "STRUCTURE_1j1a", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|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>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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>
+or leave the SCENE parameter empty for the default display.
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+-->
-|DOMAIN=
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-|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>
-}}
 '''PANCREATIC SECRETORY PHOSPHOLIPASE A2 (IIa) WITH ANTI-INFLAMMATORY ACTIVITY'''
@@ Line 24: / Line 21: @@
 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:[http://www.ncbi.nlm.nih.gov/pubmed/12616631 12616631]
 [[Category: Homo sapiens]]
-[[Category: Phospholipase A(2)]]
 [[Category: Single protein]]
 [[Category: Clark, C I.]]
@@ Line 36: / Line 32: @@
 [[Category: Tyndall, J D.A.]]
 [[Category: Whitehouse, M W.]]
-[[Category: enzyme inhibitor]]
+[[Category: Enzyme inhibitor]]
-[[Category: inflammation]]
+[[Category: Inflammation]]
-[[Category: medicinal chemistry]]
+[[Category: Medicinal chemistry]]
-[[Category: structure-activity relationship]]
+[[Category: Structure-activity relationship]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 20:40:41 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:27:35 2008''