Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c)

Ming W. Shi; Alexandre N. Sobolev; Tanja Schirmeister; Bernd Engels; Thomas C. Schmidt; Peter Luger; Stefan Mebs; Birger Dittrich; Yu Sheng Chen; Joanna M. Bąk; Dylan Jayatilaka; Charles S. Bond; Michael J. Turner; Scott G. Stewart; Mark A. Spackman; Simon Grabowsky

doi:10.1039/c4nj01503g

Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c)

Ming W. Shi, Alexandre N. Sobolev, Tanja Schirmeister, Bernd Engels, Thomas C. Schmidt, Peter Luger, Stefan Mebs, Birger Dittrich, Yu Sheng Chen, Joanna M. Bąk, Dylan Jayatilaka, Charles S. Bond, Michael J. Turner, Scott G. Stewart, Mark A. Spackman, Simon Grabowsky

School of Molecular Sciences

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Abstract

After a long history of use as a prototype cysteine protease inhibitor, the crystal structure of loxistatin acid (E64c) is finally determined experimentally using intense synchrotron radiation, providing insight into how the inherent electronic nature of this protease inhibitor molecule determines its biochemical activity. Based on the striking similarity of its intermolecular interactions with those observed in a biological environment, the electrostatic potential of crystalline E64c is used to map the characteristics of a pseudo-enzyme pocket.

Original language	English
Pages (from-to)	1628-1633
Number of pages	6
Journal	New Journal of Chemistry
Volume	39
Issue number	3
DOIs	https://doi.org/10.1039/c4nj01503g
Publication status	Published - 1 Mar 2015

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10.1039/c4nj01503g

Shi et al Electrostatic complementarity in pseudoreceptor modeling (2015)Accepted author manuscript, 828 KB

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Shi, M. W., Sobolev, A. N., Schirmeister, T., Engels, B., Schmidt, T. C., Luger, P., Mebs, S., Dittrich, B., Chen, Y. S., Bąk, J. M., Jayatilaka, D., Bond, C. S., Turner, M. J., Stewart, S. G., Spackman, M. A., & Grabowsky, S. (2015). Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c). New Journal of Chemistry, 39(3), 1628-1633. https://doi.org/10.1039/c4nj01503g

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title = "Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c)",

abstract = "After a long history of use as a prototype cysteine protease inhibitor, the crystal structure of loxistatin acid (E64c) is finally determined experimentally using intense synchrotron radiation, providing insight into how the inherent electronic nature of this protease inhibitor molecule determines its biochemical activity. Based on the striking similarity of its intermolecular interactions with those observed in a biological environment, the electrostatic potential of crystalline E64c is used to map the characteristics of a pseudo-enzyme pocket.",

author = "Shi, {Ming W.} and Sobolev, {Alexandre N.} and Tanja Schirmeister and Bernd Engels and Schmidt, {Thomas C.} and Peter Luger and Stefan Mebs and Birger Dittrich and Chen, {Yu Sheng} and B{\c a}k, {Joanna M.} and Dylan Jayatilaka and Bond, {Charles S.} and Turner, {Michael J.} and Stewart, {Scott G.} and Spackman, {Mark A.} and Simon Grabowsky",

year = "2015",

month = mar,

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doi = "10.1039/c4nj01503g",

language = "English",

volume = "39",

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journal = "New Journal of Chemistry",

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publisher = "ROYAL SOC CHEMISTRY",

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Shi, MW, Sobolev, AN, Schirmeister, T, Engels, B, Schmidt, TC, Luger, P, Mebs, S, Dittrich, B, Chen, YS, Bąk, JM, Jayatilaka, D , Bond, CS, Turner, MJ, Stewart, SG , Spackman, MA & Grabowsky, S 2015, 'Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c)', New Journal of Chemistry, vol. 39, no. 3, pp. 1628-1633. https://doi.org/10.1039/c4nj01503g

TY - JOUR

T1 - Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures

T2 - The case of loxistatin acid (E64c)

AU - Shi, Ming W.

AU - Sobolev, Alexandre N.

AU - Schirmeister, Tanja

AU - Engels, Bernd

AU - Schmidt, Thomas C.

AU - Luger, Peter

AU - Mebs, Stefan

AU - Dittrich, Birger

AU - Chen, Yu Sheng

AU - Bąk, Joanna M.

AU - Jayatilaka, Dylan

AU - Bond, Charles S.

AU - Turner, Michael J.

AU - Stewart, Scott G.

AU - Spackman, Mark A.

AU - Grabowsky, Simon

PY - 2015/3/1

Y1 - 2015/3/1

N2 - After a long history of use as a prototype cysteine protease inhibitor, the crystal structure of loxistatin acid (E64c) is finally determined experimentally using intense synchrotron radiation, providing insight into how the inherent electronic nature of this protease inhibitor molecule determines its biochemical activity. Based on the striking similarity of its intermolecular interactions with those observed in a biological environment, the electrostatic potential of crystalline E64c is used to map the characteristics of a pseudo-enzyme pocket.

AB - After a long history of use as a prototype cysteine protease inhibitor, the crystal structure of loxistatin acid (E64c) is finally determined experimentally using intense synchrotron radiation, providing insight into how the inherent electronic nature of this protease inhibitor molecule determines its biochemical activity. Based on the striking similarity of its intermolecular interactions with those observed in a biological environment, the electrostatic potential of crystalline E64c is used to map the characteristics of a pseudo-enzyme pocket.

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U2 - 10.1039/c4nj01503g

DO - 10.1039/c4nj01503g

M3 - Article

SN - 1144-0546

VL - 39

SP - 1628

EP - 1633

JO - New Journal of Chemistry

JF - New Journal of Chemistry

IS - 3

ER -

Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c)

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Electrostatic Complementarity - A Unifying Principle in Molecular Crystal Structures

Seeing Chemical Reactions: Electron Pairing and Energetics Along Pseudo-Reaction Pathways From High-Resolution X-Ray Diffraction Data

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Electrostatic complementarity in pseudoreceptor modeling based on drug molecule crystal structures: The case of loxistatin acid (E64c)

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Electrostatic Complementarity - A Unifying Principle in Molecular Crystal Structures

Seeing Chemical Reactions: Electron Pairing and Energetics Along Pseudo-Reaction Pathways From High-Resolution X-Ray Diffraction Data

Cite this