Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome

Michael Groll; Celia R. Berkers; Hidde L. Ploegh; Huib Ovaa

doi:10.1016/j.str.2005.11.019

Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome

Michael Groll, Celia R. Berkers, Hidde L. Ploegh, Huib Ovaa

Research output: Contribution to journal › Article › peer-review

424 Scopus citations

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.

Original language	English
Pages (from-to)	451-456
Number of pages	6
Journal	Structure
Volume	14
Issue number	3
DOIs	https://doi.org/10.1016/j.str.2005.11.019
State	Published - Mar 2006
Externally published	Yes

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10.1016/j.str.2005.11.019

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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{\textregistered}, 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.",

author = "Michael Groll and Berkers, {Celia R.} and Ploegh, {Hidde L.} and Huib Ovaa",

note = "Funding Information: We are grateful to Gleb Bourenkov for his valuable help during crystal measurements at the Deutsche Electronen Synchrotron facilities in Hamburg. This work was supported by grants from The Netherlands Organization for Scientific Research (NWO) and the Dutch Cancer Society (KWF) to H.O., and by support from the NIH to H.P. ",

year = "2006",

month = mar,

doi = "10.1016/j.str.2005.11.019",

language = "English",

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journal = "Structure",

issn = "0969-2126",

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T1 - Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome

AU - Groll, Michael

AU - Berkers, Celia R.

AU - Ploegh, Hidde L.

AU - Ovaa, Huib

N1 - Funding Information: We are grateful to Gleb Bourenkov for his valuable help during crystal measurements at the Deutsche Electronen Synchrotron facilities in Hamburg. This work was supported by grants from The Netherlands Organization for Scientific Research (NWO) and the Dutch Cancer Society (KWF) to H.O., and by support from the NIH to H.P.

PY - 2006/3

Y1 - 2006/3

N2 - 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.

AB - 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.

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DO - 10.1016/j.str.2005.11.019

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SN - 0969-2126

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SP - 451

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JF - Structure

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ER -

Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome

Abstract

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