Structures, Properties, and Dynamics of Intermediates in eEF2-Diphthamide Biosynthesis

Billod, Jean-Marc (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,Göteborgs universitet; Center for Biological Research, ESP

Saenz Mendez, Patricia (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,Göteborgs Universitet; Universidad de la República, URY

Blomberg, Anders, 1956 (author): Gothenburg University,Göteborgs universitet,Institutionen för marina vetenskaper,Department of marine sciences

Eriksson, Leif A, 1964 (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

(creator_code:org_t)

2016-08-24
2016
English.
In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 56:9, s. 1776-1786

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; https://urn.kb.se/re...; show less...

Abstract Subject headings

The eukaryotic translation Elongation Factor 2 (eEF2) is an essential enzyme in protein synthesis. eEF2 contains a unique modification of a histidine (His699 in yeast; HIS) into diphthamide (DTA), obtained via 3-amino-3-carboxypropyl (ACP) and diphthine (DTI) intermediates in the biosynthetic pathway. This essential and unique modification is also vulnerable, in that it can be efficiently targeted by NAD(+)-dependent ADP-ribosylase toxins, such as diphtheria toxin (DT). However, none of the intermediates in the biosynthesis path is equally vulnerable against the toxins. This study aims to address the different susceptibility of DTA and its precursors against bacterial toxins. We have herein undertaken a detailed in silico study of the structural features and dynamic motion of different His699 intermediates along the diphthamide synthesis pathway (HIS, ACP, DTI, DTA). The study points out that DTA forms a strong hydrogen bond with an asparagine which might explain the ADP-ribosylation mechanism caused by the diphtheria toxin (DT). Finally, in silico mutagenesis studies were performed on the DTA modified protein, in order to hamper the formation of such a hydrogen bond. The results indicate that the mutant structure might in fact be less susceptible to attack by DT and thereby behave similarly to DTI in this respect.

NATURVETENSKAP -- Kemi (hsv//swe)
NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
NATURVETENSKAP -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)
NATURAL SCIENCES -- Computer and Information Sciences -- Bioinformatics (hsv//eng)

By the author/editor: Billod, Jean-Mar ...; Saenz Mendez, Pa ...; Blomberg, Anders ...; Eriksson, Leif A ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Computer and Inf ...; and Bioinformatics

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.