Imperial College London
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ProfessorXiaodongZhang

Faculty of Medicine, Department of Infectious Disease

Professor of Macromolecular Structure and Function
 
 
 
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Contact

 

+44 (0)20 7594 3151xiaodong.zhang Website

 
 
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Assistant

 

Miss Kelly Butler +44 (0)20 7594 2763

 
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Location

 

104Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stach:2020:10.1002/1873-3468.13667,
author = {Stach, L and Morgan, RM and Makhlouf, L and Douangamath, A and von, Delft F and Zhang, X and Freemont, PS},
doi = {10.1002/1873-3468.13667},
journal = {FEBS Letters},
pages = {933--943},
title = {Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split-washer-type mechanism for substrate unfolding},
url = {http://dx.doi.org/10.1002/1873-3468.13667},
volume = {594},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Several pathologies have been associated with the AAA+ ATPase p97, an enzyme essential to protein homeostasis. Heterozygous polymorphisms in p97 have been shown to cause neurological disease, while elevated proteotoxic stress in tumours has made p97 an attractive cancer chemotherapy target. The cellular processes reliant on p97 are well described. Highresolution structural models of its catalytic D2 domain, however, have proved elusive, as has the mechanism by which p97 converts the energy from ATP hydrolysis into mechanical force to unfold protein substrates. Here, we describe the highresolution structure of the p97 D2 ATPase domain. This crystal system constitutes a valuable tool for p97 inhibitor development and identifies a potentially druggable pocket in the D2 domain. In addition, its P61 symmetry suggests a mechanism for substrate unfolding by p97.
AU  - Stach,L
AU  - Morgan,RM
AU  - Makhlouf,L
AU  - Douangamath,A
AU  - von,Delft F
AU  - Zhang,X
AU  - Freemont,PS
DO  - 10.1002/1873-3468.13667
EP  - 943
PY  - 2020///
SN  - 0014-5793
SP  - 933
TI  - Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split-washer-type mechanism for substrate unfolding
T2  - FEBS Letters
UR  - http://dx.doi.org/10.1002/1873-3468.13667
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000497897200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13667
UR  - http://hdl.handle.net/10044/1/75589
VL  - 594
ER  -
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