Mechanistic insights into the reductive dehydroxylation pathway for the biosynthesis of isoprenoids promoted by the IspH enzyme.

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 terpenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), promoted by the IspH enzyme. Our results support the viability of the bio-organometallic pathway through rotation of the OH group of HMBPP away from the [Fe₄S₄] cluster at the core of the catalytic site, to become engaged in a H-bond with Glu126. This rotation is synchronous with π-coordination of the C2[double bond, length as m-dash]C3 double bond of HMBPP to the apical Fe atom of the [Fe₄S₄]

SUBMITTER: Abdel-Azeim S 

PROVIDER: S-EPMC5511988 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature