2fak: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
|SITE= | |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> | |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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1ryp|1RYP]], [[1iru|1IRU]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fak OCA], [http://www.ebi.ac.uk/pdbsum/2fak PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fak RCSB]</span> | |||
}} | }} | ||
| Line 25: | Line 28: | ||
[[Category: Groll, M.]] | [[Category: Groll, M.]] | ||
[[Category: Potts, B C.]] | [[Category: Potts, B C.]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
| Line 32: | Line 34: | ||
[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:00:06 2008'' | ||
Revision as of 03:00, 31 March 2008
| |||||||
| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Proteasome endopeptidase complex, with EC number 3.4.25.1 | ||||||
| Related: | 1RYP, 1IRU
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Mon Mar 31 03:00:06 2008