2ea4: Difference between revisions
New page: left|200px<br /><applet load="2ea4" size="350" color="white" frame="true" align="right" spinBox="true" caption="2ea4" /> ''''''<br /> ==About this Structure== is a [h... |
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[[Image:2ea4.jpg|left|200px]]<br /><applet load="2ea4" size="350" color="white" frame="true" align="right" spinBox="true" | [[Image:2ea4.jpg|left|200px]]<br /><applet load="2ea4" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2ea4" /> | caption="2ea4, resolution 2.35Å" /> | ||
''''''<br /> | '''h-MetAP2 complexed with A797859'''<br /> | ||
==Overview== | |||
A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were, identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2)., Small alkyl groups and 3-furyl were tolerated at the 5-position of, anthranilic acid, while -OCH(3), CH(3), and Cl were found optimal for the, 6-position. Placement of 2-aminoethoxy group at the 6-position enabled, interaction with the second Mn(2+) but did not result in enhancement in, potency. Introduction of a tertiary amino moiety at the ortho-position of, the sulfonyl phenyl ring gave reduced protein binding and improved, cellular activity, but led to lower oral bioavailability. | |||
==About this Structure== | ==About this Structure== | ||
2EA4 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=MN:'>MN</scene> and <scene name='pdbligand=F79:'>F79</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] Known structural/functional Sites: <scene name='pdbsite=AC1:Mn+Binding+Site+For+Residue+A+480'>AC1</scene>, <scene name='pdbsite=AC2:Mn+Binding+Site+For+Residue+A+481'>AC2</scene> and <scene name='pdbsite=AC3:F79+Binding+Site+For+Residue+A+482'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EA4 OCA]. | |||
[[Category: | |||
==Reference== | |||
Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids., Wang GT, Mantei RA, Kawai M, Tedrow JS, Barnes DM, Wang J, Zhang Q, Lou P, Garcia LA, Bouska J, Yates M, Park C, Judge RA, Lesniewski R, Sheppard GS, Bell RL, Bioorg Med Chem Lett. 2007 May 15;17(10):2817-22. Epub 2007 Feb 25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17350258 17350258] | |||
[[Category: Homo sapiens]] | |||
[[Category: Methionyl aminopeptidase]] | |||
[[Category: Single protein]] | |||
[[Category: Park, C.H.]] | |||
[[Category: F79]] | |||
[[Category: MN]] | |||
[[Category: hydrolase]] | |||
[[Category: protein-ligand complex]] | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 17:21:38 2008'' | ||
