Sökning: WFRF:(Kazemi Mehdi) >
Higher Flexibility ...
-
Jafari, SoniaUniversity of Kurdistan
(författare)
Higher Flexibility of Glu-172 Explains the Unusual Stereospecificity of Glyoxalase i
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
-
2018-04-10
-
American Chemical Society (ACS),2018
-
15 s.
Nummerbeteckningar
-
LIBRIS-ID:oai:lup.lub.lu.se:dced8c83-84e4-413b-950d-8d11c44a52d3
-
https://lup.lub.lu.se/record/dced8c83-84e4-413b-950d-8d11c44a52d3URI
-
https://doi.org/10.1021/acs.inorgchem.7b03215DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:art swepub-publicationtype
-
Ämneskategori:ref swepub-contenttype
Anmärkningar
-
Despite many studies during the latest two decades, the reason for the unusual stereospecificity of glyoxalase I (GlxI) is still unknown. This metalloenzyme converts both enantiomers of its natural substrate to only one enantiomer of its product. In addition, GlxI catalyzes reactions involving some substrate and product analogues with a stereospecificity similar to that of its natural substrate reaction. For example, the enzyme exchanges the pro-S, but not the pro-R, hydroxymethyl proton of glutathiohydroxyacetone (HOC-SG) with a deuterium from D2O. To find some clues to the unusual stereospecificity of GlxI, we have studied the stereospecific proton exchange of the hydroxymethyl proton of HOC-SG by this enzyme. We employed density functional theory and molecular dynamics (MD) simulations to study the proton exchange mechanism and origin of the stereospecificity. The results show that a rigid cluster model with the same flexibility for the two active-site glutamate residues cannot explain the unusual stereospecificity of GlxI. However, using a cluster model with full flexibility of Glu-172 or a larger model with the entire glutamates, extending the backbone into the neighboring residues, the results showed that there is no way for HOC-SG to exchange its protons if the alcoholic proton is directed toward Glu-99. However, if the hydroxymethyl proton instead is directed toward the more flexible Glu-172, we find a catalytic reaction mechanism for the exchange of the HS proton by a deuterium, in accordance with experimental findings. Thus, our results indicate that the special stereospecificity of GlxI is caused by the more flexible environment of Glu-172 in comparison to that of Glu-99. This higher flexibility of Glu-172 is also confirmed by MD simulations. We propose a reaction mechanism for the stereospecific proton exchange of the hydroxymethyl proton of HOC-SG by GlxI with an overall energy barrier of 15 kcal/mol.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Kazemi, NadiaUniversity of Kurdistan
(författare)
-
Ryde, UlfLund University,Lunds universitet,Beräkningskemi,Enheten för fysikalisk och teoretisk kemi,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Computational Chemistry,Physical and theoretical chemistry,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)teok-ury
(författare)
-
Irani, MehdiUniversity of Kurdistan(Swepub:lu)teok-mdi
(författare)
-
University of KurdistanBeräkningskemi
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Inorganic Chemistry: American Chemical Society (ACS)57:9, s. 4944-49580020-16691520-510X
Internetlänk
Hitta via bibliotek
Till lärosätets databas