1b6a: Difference between revisions
New page: left|200px<br /> <applet load="1b6a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b6a, resolution 1.60Å" /> '''HUMAN METHIONINE AM... |
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[[Image:1b6a.gif|left|200px]]<br /> | [[Image:1b6a.gif|left|200px]]<br /><applet load="1b6a" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1b6a, resolution 1.60Å" /> | caption="1b6a, resolution 1.60Å" /> | ||
'''HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470'''<br /> | '''HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470'''<br /> | ||
==Overview== | ==Overview== | ||
The fungal metabolite fumagillin suppresses the formation of new blood | The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 A resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design. | ||
==About this Structure== | ==About this Structure== | ||
1B6A 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 CO and TN4 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] Full crystallographic information is available from [http:// | 1B6A 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=CO:'>CO</scene> and <scene name='pdbligand=TN4:'>TN4</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B6A OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Methionyl aminopeptidase]] | [[Category: Methionyl aminopeptidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Clardy, J | [[Category: Clardy, J C.]] | ||
[[Category: Liu, S.]] | [[Category: Liu, S.]] | ||
[[Category: CO]] | [[Category: CO]] | ||
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[[Category: angiogenesis inhibitor]] | [[Category: angiogenesis inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:51:56 2008'' | ||
Revision as of 12:51, 21 February 2008
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HUMAN METHIONINE AMINOPEPTIDASE 2 COMPLEXED WITH TNP-470
OverviewOverview
The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 A resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design.
About this StructureAbout this Structure
1B6A is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Methionyl aminopeptidase, with EC number 3.4.11.18 Full crystallographic information is available from OCA.
ReferenceReference
Structure of human methionine aminopeptidase-2 complexed with fumagillin., Liu S, Widom J, Kemp CW, Crews CM, Clardy J, Science. 1998 Nov 13;282(5392):1324-7. PMID:9812898
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