1osf
From Proteopedia
(New page: 200px<br /> <applet load="1osf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1osf, resolution 1.75Å" /> '''Human Hsp90 in comp...) |
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| - | [[Image:1osf. | + | [[Image:1osf.jpg|left|200px]]<br /><applet load="1osf" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1osf" size=" | + | |
caption="1osf, resolution 1.75Å" /> | caption="1osf, resolution 1.75Å" /> | ||
'''Human Hsp90 in complex with 17-desmethoxy-17-N,N-Dimethylaminoethylamino-Geldanamycin'''<br /> | '''Human Hsp90 in complex with 17-desmethoxy-17-N,N-Dimethylaminoethylamino-Geldanamycin'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1OSF 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 KOS, MPD and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1OSF 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=KOS:'>KOS</scene>, <scene name='pdbligand=MPD:'>MPD</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: cell cycle]] | [[Category: cell cycle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:35:31 2008'' |
Revision as of 14:35, 15 February 2008
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Human Hsp90 in complex with 17-desmethoxy-17-N,N-Dimethylaminoethylamino-Geldanamycin
Overview
Hsp90 is an attractive chemotherapeutic target because it chaperones the, folding of proteins found in multiple signal transduction pathways. We, describe the 1.75 A resolution crystal structure of human Hsp90 alpha, (residues 9-236) complexed with, 17-desmethoxy-17-N,N-dimethylaminoethylamino-geldanamycin (17-DMAG). The, structure revealed an altered set of interactions between the, 17-substituent and the protein compared to geldanamycin and the, 17-dimethylaminoethyl moiety pointing into solvent, but otherwise was, similar to that reported for the complex with geldanamycin. Targeted, molecular dynamics simulations and energetic analysis indicate that, geldanamycin undergoes two major conformational changes when it binds, Hsp90, with the key step of the conversion being the trans to cis, conformational change of the macrocycle amide bond. We speculate that, 17-DMAG analogs constrained to a cis-amide in the ground state could, provide a significant increase in affinity for Hsp90.
About this Structure
1OSF is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90., Jez JM, Chen JC, Rastelli G, Stroud RM, Santi DV, Chem Biol. 2003 Apr;10(4):361-8. PMID:12725864
Page seeded by OCA on Fri Feb 15 16:35:31 2008
Categories: Homo sapiens | Single protein | Chen, J.C.H. | Jez, J.M. | Rastelli, G. | Santi, D.V. | Stroud, R.M. | ACY | KOS | MPD | Cell cycle
