4NNN: Ycp In Complex With Mg132

Citation:
Abstract
The ubiquitin-proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological and immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophilic C-terminus by which they react with the active proteolytic sites. Although the peptide moiety has attracted much attention in terms of subunit selectivity, the target specificity and biological stability of the compounds are largely determined by the reactive warheads. In this study, we have carried out a systematic investigation of described electrophiles by a combination of in vitro, in vivo, and structural methods in order to disclose the implications of altered functionality and chemical reactivity. Thereby, we were able to introduce and characterize the class of alpha-ketoamides as the most potent reversible inhibitors with possible applications for the therapy of solid tumors as well as autoimmune disorders.
PDB ID: 4NNNDownload
MMDB ID: 117527
PDB Deposition Date: 2013/11/18
Updated in MMDB: 2014/02
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4NNN: 28-meric; determined by author and by software (PISA)
Molecular Components in 4NNN
Label Count Molecule
Proteins (28 molecules)
2
Proteasome Subunit Alpha Type-2(Gene symbol: PRE8)
Molecule annotation
2
Proteasome Subunit Alpha Type-3(Gene symbol: PRE9)
Molecule annotation
2
Proteasome Subunit Alpha Type-4(Gene symbol: PRE6)
Molecule annotation
2
Proteasome Subunit Alpha Type-5(Gene symbol: PUP2)
Molecule annotation
2
Proteasome Subunit Alpha Type-6(Gene symbol: PRE5)
Molecule annotation
2
Probable Proteasome Subunit Alpha Type-7(Gene symbol: PRE10)
Molecule annotation
2
Proteasome Subunit Alpha Type-1(Gene symbol: SCL1)
Molecule annotation
2
Proteasome Subunit Beta Type-2(Gene symbol: PUP1)
Molecule annotation
2
Proteasome Subunit Beta Type-3(Gene symbol: PUP3)
Molecule annotation
2
Proteasome Subunit Beta Type-4(Gene symbol: PRE1)
Molecule annotation
2
Proteasome Subunit Beta Type-5(Gene symbol: PRE2)
Molecule annotation
2
Proteasome Subunit Beta Type-6(Gene symbol: PRE7)
Molecule annotation
2
Proteasome Subunit Beta Type-7(Gene symbol: PRE4)
Molecule annotation
2
Proteasome Subunit Beta Type-1(Gene symbol: PRE3)
Molecule annotation
Chemicals (14 molecules)
1
8
2
6
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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