1wua
From Proteopedia
(New page: 200px<br /><applet load="1wua" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wua, resolution 1.45Å" /> '''The structure of Apl...) |
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| - | [[Image:1wua.gif|left|200px]]<br /><applet load="1wua" size=" | + | [[Image:1wua.gif|left|200px]]<br /><applet load="1wua" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1wua, resolution 1.45Å" /> | caption="1wua, resolution 1.45Å" /> | ||
'''The structure of Aplyronine A-actin complex'''<br /> | '''The structure of Aplyronine A-actin complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Aplyronine A, isolated from the sea hare Aplysia kurodai, possesses an | + | Aplyronine A, isolated from the sea hare Aplysia kurodai, possesses an exceedingly potent antitumor effect in vivo and it is one of the promising candidates as an anticancer drug. This macrolide is known to depolymerize F-actin and inhibit the polymerization of actin by forming a 1:1 complex with monomeric actin. The first complex structure of actin-aplyronine A was determined via a synchrotron X-ray analysis at a 1.45 A resolution. As expected, aplyronine A binds to a hydrophobic cleft composed of subdomains 1 and 3 of actin by intercalating its aliphatic tail part into the actin molecule as do the other reported F-actin depolymerizing agents. Unexpectedly, this complex structure shows the specific structural features around the trimethylserine moiety, revealed as an important moiety of aplyronine A for cytotoxicity against HeLa cells. Combining this result and our previous one, the moiety should strongly relate to the specific biological activity of aplyronine A; i.e. a potent antitumor effect. |
==About this Structure== | ==About this Structure== | ||
| - | 1WUA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with CA, ATP and AP8 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1WUA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=AP8:'>AP8</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WUA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: potent antitumor effect]] | [[Category: potent antitumor effect]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:48:17 2008'' |
Revision as of 13:48, 21 February 2008
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The structure of Aplyronine A-actin complex
Overview
Aplyronine A, isolated from the sea hare Aplysia kurodai, possesses an exceedingly potent antitumor effect in vivo and it is one of the promising candidates as an anticancer drug. This macrolide is known to depolymerize F-actin and inhibit the polymerization of actin by forming a 1:1 complex with monomeric actin. The first complex structure of actin-aplyronine A was determined via a synchrotron X-ray analysis at a 1.45 A resolution. As expected, aplyronine A binds to a hydrophobic cleft composed of subdomains 1 and 3 of actin by intercalating its aliphatic tail part into the actin molecule as do the other reported F-actin depolymerizing agents. Unexpectedly, this complex structure shows the specific structural features around the trimethylserine moiety, revealed as an important moiety of aplyronine A for cytotoxicity against HeLa cells. Combining this result and our previous one, the moiety should strongly relate to the specific biological activity of aplyronine A; i.e. a potent antitumor effect.
About this Structure
1WUA is a Single protein structure of sequence from Oryctolagus cuniculus with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structure basis for antitumor effect of aplyronine a., Hirata K, Muraoka S, Suenaga K, Kuroda T, Kato K, Tanaka H, Yamamoto M, Takata M, Yamada K, Kigoshi H, J Mol Biol. 2006 Mar 3;356(4):945-54. Epub 2005 Dec 27. PMID:16406066
Page seeded by OCA on Thu Feb 21 15:48:17 2008
Categories: Oryctolagus cuniculus | Single protein | Hirata, K. | Kato, K. | Kigoshi, H. | Kuroda, T. | Muraoka, S. | Suenaga, K. | Takata, M. | Tanaka, H. | Yamada, K. | Yamamoto, M. | AP8 | ATP | CA | Aplyronine a | Macrolide | Marine sponge | Potent antitumor effect
