1j1a: Difference between revisions
New page: left|200px<br /> <applet load="1j1a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1j1a, resolution 2.20Å" /> '''PANCREATIC SECRETOR... |
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[[Image:1j1a.gif|left|200px]]<br /> | [[Image:1j1a.gif|left|200px]]<br /><applet load="1j1a" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1j1a, resolution 2.20Å" /> | caption="1j1a, resolution 2.20Å" /> | ||
'''PANCREATIC SECRETORY PHOSPHOLIPASE A2 (IIa) WITH ANTI-INFLAMMATORY ACTIVITY'''<br /> | '''PANCREATIC SECRETORY PHOSPHOLIPASE A2 (IIa) WITH ANTI-INFLAMMATORY ACTIVITY'''<br /> | ||
==Overview== | ==Overview== | ||
Few reported inhibitors of secretory phospholipase A(2) enzymes truly | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1J1A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and BHP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1J1A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=BHP:'>BHP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J1A OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Clark, C | [[Category: Clark, C I.]] | ||
[[Category: Fairlie, D | [[Category: Fairlie, D P.]] | ||
[[Category: Guthrie, T.]] | [[Category: Guthrie, T.]] | ||
[[Category: Hansford, K | [[Category: Hansford, K A.]] | ||
[[Category: Martin, J | [[Category: Martin, J L.]] | ||
[[Category: McGeary, R | [[Category: McGeary, R P.]] | ||
[[Category: Reid, R | [[Category: Reid, R C.]] | ||
[[Category: Schafer, K.]] | [[Category: Schafer, K.]] | ||
[[Category: Tyndall, J | [[Category: Tyndall, J D.A.]] | ||
[[Category: Whitehouse, M | [[Category: Whitehouse, M W.]] | ||
[[Category: BHP]] | [[Category: BHP]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: structure-activity relationships]] | [[Category: structure-activity relationships]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:17:55 2008'' | ||
Revision as of 14:17, 21 February 2008
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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.
DiseaseDisease
Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[172411]
About this StructureAbout this Structure
1J1A is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 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
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