2F16

Crystal structure of the yeast 20S proteasome in complex with bortezomib

PDB DOI: https://doi.org/10.2210/pdb2F16/pdb

Classification: HYDROLASE
Organism(s): Saccharomyces cerevisiae
Mutation(s): No

Deposited: 2005-11-14 Released: 2006-03-21
Deposition Author(s): Groll, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.80 Å
R-Value Free: 0.264
R-Value Work: 0.231
R-Value Observed: 0.231

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

This is version 1.4 of the entry. See complete history.

Literature

Crystal Structure of the Boronic Acid-Based Proteasome Inhibitor Bortezomib in Complex with the Yeast 20S Proteasome.

Groll, M., Berkers, C.R., Ploegh, H.L., Ovaa, H.

(2006) Structure 14: 451-456

PubMed: 16531229 Search on PubMed
DOI: https://doi.org/10.1016/j.str.2005.11.019
Primary Citation of Related Structures:
2F16

PubMed 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.

Organizational Affiliation

Department for Physiological Chemistry, Ludwig-Maximilians-University, Butenandtstrasse 5, Building B 81377, München, Germany. [email protected]

Macromolecule Content

Total Structure Weight: 706.51 kDa
Atom Count: 50,753
Modelled Residue Count: 6,368
Deposited Residue Count: 6,368
Unique protein chains: 14

Macromolecules

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Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component Y7	A, O	250	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P23639 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P23639 Go to UniProtKB: P23639
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P23639
Sequence Annotations Expand
Reference Sequence

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Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component Y13	B, P	244	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P23638 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P23638 Go to UniProtKB: P23638
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P23638
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Reference Sequence

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Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PRE6	C, Q	241	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P40303 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P40303 Go to UniProtKB: P40303
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P40303
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Reference Sequence

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Entity ID: 4
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PUP2	D, R	242	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P32379 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P32379 Go to UniProtKB: P32379
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P32379
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Reference Sequence

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Entity ID: 5
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PRE5	E, S	233	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P40302 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P40302 Go to UniProtKB: P40302
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P40302
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Reference Sequence

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Entity ID: 6
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component C1	F, T	244	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P21242 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P21242 Go to UniProtKB: P21242
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P21242
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Reference Sequence

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Entity ID: 7
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component C7-alpha	G, U	243	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P21243 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P21243 Go to UniProtKB: P21243
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P21243
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Reference Sequence

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Entity ID: 8
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PUP1	H, V	222	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P25043 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P25043 Go to UniProtKB: P25043
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P25043
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Reference Sequence

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Entity ID: 9
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PUP3	I, W	204	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P25451 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P25451 Go to UniProtKB: P25451
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P25451
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Reference Sequence

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Entity ID: 10
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component C11	J, X	198	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P22141 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P22141 Go to UniProtKB: P22141
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P22141
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Reference Sequence

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Entity ID: 11
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PRE2	K, Y	212	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P30656 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P30656 Go to UniProtKB: P30656
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P30656
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Reference Sequence

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Entity ID: 12
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component C5	L, Z	222	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P23724 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P23724 Go to UniProtKB: P23724
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P23724
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Reference Sequence

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Entity ID: 13
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PRE4	AA [auth 1], M	233	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P30657 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P30657 Go to UniProtKB: P30657
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P30657
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Reference Sequence

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Entity ID: 14
Molecule	Chains	Sequence Length	Organism	Details	Image
Proteasome component PRE3	BA [auth 2], N	196	Saccharomyces cerevisiae	Mutation(s): 0 EC: 3.4.25.1
UniProt
Find proteins for P38624 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c)) Explore P38624 Go to UniProtKB: P38624
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Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P38624
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Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
BO2 Query on BO2 Download Ideal Coordinates CCD File SDF format, chain CA [auth H] SDF format, chain DA [auth K] SDF format, chain EA [auth N] SDF format, chain FA [auth V] SDF format, chain GA [auth Y] SDF format, chain HA [auth 2] MOL2 format, chain CA [auth H] MOL2 format, chain DA [auth K] MOL2 format, chain EA [auth N] MOL2 format, chain FA [auth V] MOL2 format, chain GA [auth Y] MOL2 format, chain HA [auth 2] mmCIF format, chain CA [auth H] mmCIF format, chain DA [auth K] mmCIF format, chain EA [auth N] mmCIF format, chain FA [auth V] mmCIF format, chain GA [auth Y] mmCIF format, chain HA [auth 2]	CA [auth H] DA [auth K] EA [auth N] FA [auth V] GA [auth Y] CA [auth H], DA [auth K], EA [auth N], FA [auth V], GA [auth Y], HA [auth 2]	N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE C₁₉ H₂₅ B N₄ O₄ GXJABQQUPOEUTA-RDJZCZTQSA-N		Interactions Focus chain CA [auth H] Focus chain DA [auth K] Focus chain EA [auth N] Focus chain FA [auth V] Focus chain GA [auth Y] Focus chain HA [auth 2]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.80 Å
R-Value Free: 0.264
R-Value Work: 0.231
R-Value Observed: 0.231
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 136.175	α = 90
b = 300.716	β = 113.28
c = 144.659	γ = 90

Software Package:

Software Name	Purpose
CNS	refinement
DENZO	data reduction
SCALEPACK	data scaling
CNS	phasing

Structure Validation

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Entry History

Deposition Data

Released Date: 2006-03-21

Deposition Author(s):

Groll, M.

Revision History (Full details and data files)

Version 1.0: 2006-03-21
Type: Initial release
Version 1.1: 2008-04-29
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Derived calculations, Version format compliance
Version 1.3: 2023-08-23
Changes: Data collection, Database references, Derived calculations, Refinement description
Version 1.4: 2024-10-30
Changes: Structure summary

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.

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Help and Resources

2F16

Crystal structure of the yeast 20S proteasome in complex with bortezomib

Crystal Structure of the Boronic Acid-Based Proteasome Inhibitor Bortezomib in Complex with the Yeast 20S Proteasome.

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Experimental Data

Structure Validation

Deposition Data

Revision History (Full details and data files)