2F16
Target information
- RCSB PDB
- 2F16
- Title
- Crystal structure of the yeast 20S proteasome in complex with bortezomib
- Method
- X-RAY DIFFRACTION
- Resolution
- 2.8
- Classification
- HYDROLASE
- Organism
- Saccharomyces cerevisiae
- Protein
- Proteasome subunit beta type-2 (P25043)
- Year
- 2006
- Publication Title
- Crystal Structure of the Boronic Acid-Based Proteasome Inhibitor Bortezomib in Complex with the Yeast 20S Proteasome.
- Abstract
-
The dipeptide boronic acid bortezomib, also termed VELCADE, is a proteasome inhibitor now in use for the treatment of multiple myeloma, and its use for the treatment of other malignancies is being explored. We determined the crystal structure of the yeast 20S proteasome in complex with bortezomib to establish the specificity and binding mode of bortezomib to the proteasome's different catalytically active sites. This structure should enable the rational design of new boronic acid derivatives with improved affinities and specificities for individual active subunits.
- External Link
- RCSB PDB
Ligand information
- HET
- BO2
- Chain ID
- H
- HET Number
- 1400
- Molecular Formula
- C19H25BN4O4
- Structure
-
- IUPAC Name
- [(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid
- InChI
- InChI=1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17-/m0/s1
- InChI Key
- GXJABQQUPOEUTA-RDJZCZTQSA-N
- Canonical SMILES
- CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1cnccn1)B(O)O
- Bioactivity data
- CI006008
Covalent Binding
- Warhead
- Boronic Acid
- Reaction Mechanism
- Boronic Acid Addition
- Residue
- THR : 1
- Residue Chain
- H
- Interactions
- Pharmacophore Model