1kqu: Difference between revisions
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New page: left|200px<br /> <applet load="1kqu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kqu, resolution 2.10Å" /> '''Human phospholipase... |
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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. | ||
==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: structure]] | [[Category: structure]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:53:48 2007'' | ||
