Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.

Molecular angler fish: By precisely positioning different binding ligands (L) around the active site "mouth" of a degradative proteinase enzyme, target proteins (TP) can be plucked from solution, locked in position adjacent to the catalytic triad "jaws", and in this way readily a...

Full description

Bibliographic Details
Main Authors: Davis, B, Sala, R, Hodgson, DR, Ullman, A, Khumtaveeporn, K, Estell, D, Sanford, K, Bott, R, Jones, J
Format: Journal article
Language:English
Published: 2003
_version_ 1826260247134601216
author Davis, B
Sala, R
Hodgson, DR
Ullman, A
Khumtaveeporn, K
Estell, D
Sanford, K
Bott, R
Jones, J
author_facet Davis, B
Sala, R
Hodgson, DR
Ullman, A
Khumtaveeporn, K
Estell, D
Sanford, K
Bott, R
Jones, J
author_sort Davis, B
collection OXFORD
description Molecular angler fish: By precisely positioning different binding ligands (L) around the active site "mouth" of a degradative proteinase enzyme, target proteins (TP) can be plucked from solution, locked in position adjacent to the catalytic triad "jaws", and in this way readily and specifically degraded (see scheme). In this strategy, the appropriate ligand acts as a homing device to confer and enhance selectivity, in the best case by more than 350-fold, in a generic process that exploits the intrinsic, ligand-recognition capabilities of the protein target to trigger its own destruction. The hunting strategy of the deep sea Angler Fish, which uses a lure above its mouth, illustrates this principle.
first_indexed 2024-03-06T19:02:37Z
format Journal article
id oxford-uuid:140feb3f-b319-417d-b78c-4f691323ad67
institution University of Oxford
language English
last_indexed 2024-03-06T19:02:37Z
publishDate 2003
record_format dspace
spelling oxford-uuid:140feb3f-b319-417d-b78c-4f691323ad672022-03-26T10:17:26ZSelective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:140feb3f-b319-417d-b78c-4f691323ad67EnglishSymplectic Elements at Oxford2003Davis, BSala, RHodgson, DRUllman, AKhumtaveeporn, KEstell, DSanford, KBott, RJones, JMolecular angler fish: By precisely positioning different binding ligands (L) around the active site "mouth" of a degradative proteinase enzyme, target proteins (TP) can be plucked from solution, locked in position adjacent to the catalytic triad "jaws", and in this way readily and specifically degraded (see scheme). In this strategy, the appropriate ligand acts as a homing device to confer and enhance selectivity, in the best case by more than 350-fold, in a generic process that exploits the intrinsic, ligand-recognition capabilities of the protein target to trigger its own destruction. The hunting strategy of the deep sea Angler Fish, which uses a lure above its mouth, illustrates this principle.
spellingShingle Davis, B
Sala, R
Hodgson, DR
Ullman, A
Khumtaveeporn, K
Estell, D
Sanford, K
Bott, R
Jones, J
Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.
title Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.
title_full Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.
title_fullStr Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.
title_full_unstemmed Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.
title_short Selective protein degradation by ligand-targeted enzymes: towards the creation of catalytic antagonists.
title_sort selective protein degradation by ligand targeted enzymes towards the creation of catalytic antagonists
work_keys_str_mv AT davisb selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT salar selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT hodgsondr selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT ullmana selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT khumtaveepornk selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT estelld selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT sanfordk selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT bottr selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists
AT jonesj selectiveproteindegradationbyligandtargetedenzymestowardsthecreationofcatalyticantagonists