Crystal structure of isopentenyl diphosphate:dimethylallyl diphosphate isomerase

Abstract

Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase catalyses a crucial activation step in the isoprenoid biosynthesis pathway. This enzyme is responsible for the isomerization of the carbon±carbon double bond of IPP to create the potent electrophile DMAPP. DMAPP then alkylates other molecules, including IPP, to initiate the extraordinary variety of isoprenoid compounds found in nature. The crystal structures of free and metal-bound Escherichia coli IPP isomerase reveal critical active site features underlying its catalytic mechanism. The enzyme requires one Mn 2+ or Mg 2+ ion to fold in its active conformation, forming a distorted octahedral metal coordination site composed of three histidines and two glutamates and located in the active site. Two critical residues, C67 and E116, face each other within the active site, close to the metal-binding site. The structures are compatible with a mechanism in which the cysteine initiates the reaction by protonating the carbon±carbon double bond, with the antarafacial rearrangement ultimately achieved by one of the glutamates involved in the metal coordination sphere. W161 may stabilize the highly reactive carbocation generated during the reaction through quadrupole± charge interaction.

Determination of Kinetics and the Crystal Structure of a Novel Type 2 Isopentenyl Diphosphate: Dimethylallyl Diphosphate Isomerase fromStreptococcus pneumoniae

“…[5–8] A second convergently evolved isoform (IDI-2), found in plant chloroplasts and many bacteria, was discovered in 2001 and requires reduced flavin mononucleotide and MgCl 2 as cofactors. [9] In 2007, Rothman et al proposed a mechanism for the isomerization where the reduced flavin cofactor acts as a general acid/base catalyst for protonation of IPP and deprotonation of the resulting carbocationic intermediate.…”

Crystal Structure of Type 2 Isopentenyl Diphosphate Isomerase from Thermus thermophilus in Complex with Inorganic Pyrophosphate

“…3,4, 5 The structure of IDI-1 is known, and its mechanism of action has been studied extensively. 6-8 The IDI-2 isoform was discovered recently. 9 The enzyme is a flavoprotein that requires FMN, a reducing agent (typically NADPH), and a divalent metal.…”

Theoretically predicted structures of plasma membrane Ca2+-ATPase and their susceptibilities to oxidation

“…For I-23, the one template ascertained was a human monocyte chemoattractant protein (1DOK chain A) [40]. For CT, the three templates included the yeast initiation factor 4A N-terminal domain (1QVA) [41], the E. coli metal-free isopentenyl diphosphate:dimethylallyl diphosphate isomerase (1HZT) [42], and the pyruvate kinase from rabbit muscle (1A49 chain A) [43]. In addition to the above list of templates, a structural model of the aforementioned C20W-CaM complex (PDB entry 1CFF) as resolved via NMR measurements [31] was used as a template in constructing the CT model.…”