1kqu
From Proteopedia
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|PDB= 1kqu |SIZE=350|CAPTION= <scene name='initialview01'>1kqu</scene>, resolution 2.10Å | |PDB= 1kqu |SIZE=350|CAPTION= <scene name='initialview01'>1kqu</scene>, resolution 2.10Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=BR4:6-PHENYL-4(R)-(7-PHENYL-HEPTANOYLAMINO)-HEXANOIC+ACID'>BR4</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=[[1d4k|1D4K]], [[1d4l|1D4L]], [[1kqt|1KQT]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kqu OCA], [http://www.ebi.ac.uk/pdbsum/1kqu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kqu 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=172411 172411]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Martin, J L.]] | [[Category: Martin, J L.]] | ||
[[Category: Tyndall, J D.]] | [[Category: Tyndall, J D.]] | ||
| - | [[Category: BR4]] | ||
| - | [[Category: CA]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
[[Category: phospholipase a2]] | [[Category: phospholipase a2]] | ||
[[Category: structure]] | [[Category: structure]] | ||
| - | ''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 21:52:17 2008'' |
Revision as of 18:52, 30 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Phospholipase A(2), with EC number 3.1.1.4 | ||||||
| Related: | 1D4K, 1D4L, 1KQT
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human phospholipase A2 complexed with a substrate anologue
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.
About this Structure
1KQU is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 21:52:17 2008
