From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2fhh.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:2fhh.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2fhh| PDB=2fhh | SCENE= }} | | {{STRUCTURE_2fhh| PDB=2fhh | SCENE= }} |
| | | | |
| - | '''Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with a peptidyl boronate inhibitor MLN-273'''
| + | ===Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with a peptidyl boronate inhibitor MLN-273=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Mycobacterium tuberculosis (Mtb) has the remarkable ability to resist killing by human macrophages. The 750 kDa proteasome, not available in most eubacteria except Actinomycetes, appears to contribute to Mtb's resistance. The crystal structure of the Mtb proteasome at 3.0 A resolution reveals a substrate-binding pocket with composite features of the distinct beta1, beta2 and beta5 substrate binding sites of eukaryotic proteasomes, accounting for the broad specificity of the Mtb proteasome towards oligopeptides described in the companion article [Lin et al. (2006), Mol Microbiol doi:10.1111/j.1365-2958.2005.05035.x]. The substrate entrance at the end of the cylindrical proteasome appears open in the crystal structure due to partial disorder of the alpha-subunit N-terminal residues. However, cryo-electron microscopy of the core particle reveals a closed end, compatible with the density observed in negative-staining electron microscopy that depended on the presence of the N-terminal octapetides of the alpha-subunits in the companion article, suggesting that the Mtb proteasome has a gated structure. We determine for the first time the proteasomal inhibition mechanism of the dipeptidyl boronate N-(4-morpholine)carbonyl-beta-(1-naphthyl)-L-alanine-L-leucine boronic acid (MLN-273), an analogue of the antimyeloma drug bortezomib. The structure improves prospects for designing Mtb-specific proteasomal inhibitors as a novel approach to chemotherapy of tuberculosis.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16468986}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16468986 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_16468986}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 25: |
Line 29: |
| | [[Category: Inhibitor-complex]] | | [[Category: Inhibitor-complex]] |
| | [[Category: Multi-subunit protein assembly]] | | [[Category: Multi-subunit protein assembly]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:54:11 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:38:17 2008'' |
Revision as of 17:38, 28 July 2008
Template:STRUCTURE 2fhh
Crystal Structure of Mycobacterium Tuberculosis Proteasome in complex with a peptidyl boronate inhibitor MLN-273
Template:ABSTRACT PUBMED 16468986
About this Structure
2FHH is a Protein complex structure of sequences from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Structure of the Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate., Hu G, Lin G, Wang M, Dick L, Xu RM, Nathan C, Li H, Mol Microbiol. 2006 Mar;59(5):1417-28. PMID:16468986
Page seeded by OCA on Mon Jul 28 20:38:17 2008
