Sökning: onr:"swepub:oai:DiVA.org:lnu-50610" >
Computational desig...
Computational design of enone-binding proteins with catalytic activity for the Morita-Baylis-Hillman reaction
-
- Bjelic, Sinisa (författare)
- University of Washington, USA
-
- Nivón, Lucas G (författare)
- University of Washington, USA
-
- Çelebi-Ölçüm, Nihan (författare)
- University of California, USA ; Yeditepe University, Turkey
-
visa fler...
-
- Kiss, Gert (författare)
- University of California, USA
-
Rosewall, Carolyn F (författare)
-
Lovick, Helena M (författare)
-
Ingalls, Erica L (författare)
-
- Gallaher, Jasmine Lynn (författare)
- University of Washington, USA
-
- Seetharaman, Jayaraman (författare)
- Columbia University, USA
-
- Lew, Scott (författare)
- Columbia University, USA
-
- Montelione, Gaetano Thomas (författare)
- Columbia University, USA
-
- Hunt, John Francis (författare)
- Columbia University, USA
-
Michael, Forrest Edwin (författare)
-
- Houk, K N (författare)
- University of California, USA
-
- Baker, David (författare)
- University of Washington, USA
-
visa färre...
-
(creator_code:org_t)
- 2013-01-30
- 2013
- Engelska.
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:4, s. 749-757
- Relaterad länk:
-
https://europepmc.or...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- The Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociation to release the product. We used Rosetta to design 48 proteins containing active sites predicted to carry out this mechanism, of which two show catalytic activity by mass spectrometry (MS). Substrate labeling measured by MS and site-directed mutagenesis experiments show that the designed active-site residues are responsible for activity, although rate acceleration over background is modest. To characterize the designed proteins, we developed a fluorescence-based screen for intermediate formation in cell lysates, carried out microsecond molecular dynamics simulations, and solved X-ray crystal structures. These data indicate a partially formed active site and suggest several clear avenues for designing more active catalysts.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Biokemi
- Biochemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Bjelic, Sinisa
-
Nivón, Lucas G
-
Çelebi-Ölçüm, Ni ...
-
Kiss, Gert
-
Rosewall, Caroly ...
-
Lovick, Helena M
-
visa fler...
-
Ingalls, Erica L
-
Gallaher, Jasmin ...
-
Seetharaman, Jay ...
-
Lew, Scott
-
Montelione, Gaet ...
-
Hunt, John Franc ...
-
Michael, Forrest ...
-
Houk, K N
-
Baker, David
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Biokemi och mole ...
- Artiklar i publikationen
-
ACS Chemical Bio ...
- Av lärosätet
-
Linnéuniversitetet