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Structure, mechanism, and inhibition of Hedgehog acyltransferase

Abstract:

The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by the multi-pass transmembrane enzyme Hedgehog acyltransferase (HHAT). We present the high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essentia...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.molcel.2021.11.018

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Institution:
University of Oxford
Role:
Author
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Role:
Author
ORCID:
0000-0003-2961-8018
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0003-4870-5387
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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
ORCID:
0000-0001-5332-8593
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Institution:
University of Oxford
Role:
Author
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Name:
Cancer Research UK
Grant:
26752
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Name:
Medical Research Council
Grant:
MC_PC_17137
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Name:
Biotechnology & Biological Sciences Research Council
Grant:
BB/R00126X/1
Publisher:
Cell Press
Journal:
Molecular Cell More from this journal
Volume:
81
Issue:
24
Pages:
5025-5038
Publication date:
2021-12-09
Acceptance date:
2021-11-17
DOI:
EISSN:
1097-4164
ISSN:
1097-2765
Pmid:
34890564

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