2fak: Difference between revisions
New page: left|200px<br /><applet load="2fak" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fak, resolution 2.80Å" /> '''Crystal structure of... |
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[[Image:2fak.gif|left|200px]]<br /><applet load="2fak" size=" | [[Image:2fak.gif|left|200px]]<br /><applet load="2fak" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2fak, resolution 2.80Å" /> | caption="2fak, resolution 2.80Å" /> | ||
'''Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome'''<br /> | '''Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome'''<br /> | ||
==Overview== | ==Overview== | ||
The crystal structures of the yeast 20S proteasome core particle (CP) in | The crystal structures of the yeast 20S proteasome core particle (CP) in complex with Salinosporamides A (NPI-0052; 1) and B (4) were solved at <3 angstroms resolution. Each ligand is covalently bound to Thr1O(gamma) via an ester linkage to the carbonyl derived from the beta-lactone ring of the inhibitor. In the case of 1, nucleophilic addition to the beta-lactone ring is followed by addition of C-3O to the chloroethyl group, giving rise to a cyclic ether. The crystal structures were compared to that of the omuralide/CP structure solved previously, and the collective data provide new insights into the mechanism of inhibition and irreversible binding of 1. Upon opening of the beta-lactone ring, C-3O assumes the position occupied by a water molecule in the unligated enzyme and hinders deacylation of the enzyme-ligand complex. Furthermore, the resulting protonation state of Thr1NH2 deactivates the catalytic N-terminus. | ||
==About this Structure== | ==About this Structure== | ||
2FAK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with SA1 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] Full crystallographic information is available from [http:// | 2FAK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=SA1:'>SA1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FAK OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Groll, M.]] | [[Category: Groll, M.]] | ||
[[Category: Potts, B | [[Category: Potts, B C.]] | ||
[[Category: SA1]] | [[Category: SA1]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
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[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:19:28 2008'' | ||
Revision as of 18:19, 21 February 2008
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Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome
OverviewOverview
The crystal structures of the yeast 20S proteasome core particle (CP) in complex with Salinosporamides A (NPI-0052; 1) and B (4) were solved at <3 angstroms resolution. Each ligand is covalently bound to Thr1O(gamma) via an ester linkage to the carbonyl derived from the beta-lactone ring of the inhibitor. In the case of 1, nucleophilic addition to the beta-lactone ring is followed by addition of C-3O to the chloroethyl group, giving rise to a cyclic ether. The crystal structures were compared to that of the omuralide/CP structure solved previously, and the collective data provide new insights into the mechanism of inhibition and irreversible binding of 1. Upon opening of the beta-lactone ring, C-3O assumes the position occupied by a water molecule in the unligated enzyme and hinders deacylation of the enzyme-ligand complex. Furthermore, the resulting protonation state of Thr1NH2 deactivates the catalytic N-terminus.
About this StructureAbout this Structure
2FAK is a Protein complex structure of sequences from Saccharomyces cerevisiae with as ligand. Active as Proteasome endopeptidase complex, with EC number 3.4.25.1 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding., Groll M, Huber R, Potts BC, J Am Chem Soc. 2006 Apr 19;128(15):5136-41. PMID:16608349
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