Mechanistic Insights on the Reductive Dehydroxylation Pathway for the Biosynthesis of Isoprenoids Promoted by the IspH Enzyme

Handle URI:
http://hdl.handle.net/10754/558567
Title:
Mechanistic Insights on the Reductive Dehydroxylation Pathway for the Biosynthesis of Isoprenoids Promoted by the IspH Enzyme
Authors:
Abdel-Azeim, Safwat ( 0000-0001-8611-1251 ) ; Jedidi, Abdesslem ( 0000-0003-4070-3299 ) ; Cavallo, Luigi ( 0000-0002-1398-338X ) ; Eppinger, Jorg ( 0000-0001-7886-7059 )
Abstract:
Here, we report an integrated quantum mechanics/molecular mechanics (QM/MM) study of the bio-organometallic reaction pathway of the 2H+/2e- reduction of (E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate (HMBPP) into the so called universal terpenoids precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), promoted by the IspH enzyme. Our results support the viability of the bio-organometallic pathway from rotation of the OH group of HMBPP away from the [Fe4S4] cluster at the core of the catalytic site, to be engaged in a H-bond with Glu126. This rotation is synchronous with π-coordination of the C2=C3 double bond of HMBPP to the apical Fe atom of the [Fe4S4] cluster. Dehydroxylation of HMBPP is triggered by a proton transfer from Glu126 to the OH group of HMBPP. The reaction pathway is completed by competitive proton transfer from the terminal phosphate group to the C2 or C4 atom of HMBPP.
KAUST Department:
KAUST Catalysis Center (KCC); Physical Sciences and Engineering (PSE) Division
Citation:
Mechanistic Insights on the Reductive Dehydroxylation Pathway for the Biosynthesis of Isoprenoids Promoted by the IspH Enzyme 2015 Chem. Sci.
Journal:
Chem. Sci.
Issue Date:
22-Jun-2015
DOI:
10.1039/C5SC01693B
Type:
Article
ISSN:
2041-6520; 2041-6539
Additional Links:
http://pubs.rsc.org/en/Content/ArticleLanding/2015/SC/C5SC01693B
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; KAUST Catalysis Center (KCC)

Full metadata record

DC FieldValue Language
dc.contributor.authorAbdel-Azeim, Safwaten
dc.contributor.authorJedidi, Abdesslemen
dc.contributor.authorCavallo, Luigien
dc.contributor.authorEppinger, Jorgen
dc.date.accessioned2015-06-28T13:40:03Zen
dc.date.available2015-06-28T13:40:03Zen
dc.date.issued2015-06-22en
dc.identifier.citationMechanistic Insights on the Reductive Dehydroxylation Pathway for the Biosynthesis of Isoprenoids Promoted by the IspH Enzyme 2015 Chem. Sci.en
dc.identifier.issn2041-6520en
dc.identifier.issn2041-6539en
dc.identifier.doi10.1039/C5SC01693Ben
dc.identifier.urihttp://hdl.handle.net/10754/558567en
dc.description.abstractHere, we report an integrated quantum mechanics/molecular mechanics (QM/MM) study of the bio-organometallic reaction pathway of the 2H+/2e- reduction of (E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate (HMBPP) into the so called universal terpenoids precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), promoted by the IspH enzyme. Our results support the viability of the bio-organometallic pathway from rotation of the OH group of HMBPP away from the [Fe4S4] cluster at the core of the catalytic site, to be engaged in a H-bond with Glu126. This rotation is synchronous with π-coordination of the C2=C3 double bond of HMBPP to the apical Fe atom of the [Fe4S4] cluster. Dehydroxylation of HMBPP is triggered by a proton transfer from Glu126 to the OH group of HMBPP. The reaction pathway is completed by competitive proton transfer from the terminal phosphate group to the C2 or C4 atom of HMBPP.en
dc.relation.urlhttp://pubs.rsc.org/en/Content/ArticleLanding/2015/SC/C5SC01693Ben
dc.rightsArchived with thanks to Chem. Sci. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. http://creativecommons.org/licenses/by/3.0/en
dc.titleMechanistic Insights on the Reductive Dehydroxylation Pathway for the Biosynthesis of Isoprenoids Promoted by the IspH Enzymeen
dc.typeArticleen
dc.contributor.departmentKAUST Catalysis Center (KCC)en
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.identifier.journalChem. Sci.en
dc.eprint.versionPost-printen
kaust.authorAbdel-Azeim, Safwaten
kaust.authorJedidi, Abdesslemen
kaust.authorEppinger, Jorgen
kaust.authorCavallo, Luigien
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