2fak
From Proteopedia
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| - | [[Image:2fak.gif|left|200px]] | + | [[Image:2fak.gif|left|200px]] |
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| - | '''Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome''' | + | {{Structure |
| + | |PDB= 2fak |SIZE=350|CAPTION= <scene name='initialview01'>2fak</scene>, resolution 2.80Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SA1:(3AR,6R,6AS)-6-((S)-((S)-CYCLOHEX-2-ENYL)(HYDROXY)METHYL)-6A-METHYL-4-OXO-HEXAHYDRO-2H-FURO[3,2-C]PYRROLE-6-CARBALDEHYDE'>SA1</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2FAK is a [ | + | 2FAK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FAK OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16608349 16608349] |
[[Category: Proteasome endopeptidase complex]] | [[Category: Proteasome endopeptidase complex]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:50:03 2008'' |
Revision as of 14:50, 20 March 2008
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| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Proteasome endopeptidase complex, with EC number 3.4.25.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Salinosporamide A in complex with the yeast 20S proteasome
Overview
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
2FAK is a Protein complex structure of sequences from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 16:50:03 2008
