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Synthetic Biology underpins advances in the bioeconomy
Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology.
As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.
@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}
}
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 -