2ZRX: Crystal Structure Of Sulfolobus Shibatae Isopentenyl Diphosphate Isomerase In Complex With Fmn And Dmapp

Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate isomerase catalyzes isomerization between isopentenyl diphosphate and dimethylallyl diphosphate, both of which are elemental units for the biosynthesis of highly diverse isoprenoid compounds. Although the flavin cofactor is expected to be integrally involved in catalysis, its exact role remains controversial. Here we report the crystal structures of the substrate-free and complex forms of type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon Sulfolobus shibatae, not only in the oxidized state but also in the reduced state. Based on the active-site structures of the reduced FMN-substrate-enzyme ternary complexes, which are in the active state, and on the data from site-directed mutagenesis at highly conserved charged or polar amino acid residues around the active site, we demonstrate that only reduced FMN, not amino acid residues, can catalyze proton addition/elimination required for the isomerase reaction. This discovery is the first evidence for this long suspected, but previously unobserved, role of flavins just as a general acid-base catalyst without playing any redox roles, and thereby expands the known functions of these versatile coenzymes.
PDB ID: 2ZRXDownload
MMDB ID: 69123
PDB Deposition Date: 2008/9/1
Updated in MMDB: 2012/05
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 2ZRX: tetrameric; determined by author and by software (PISA)
Molecular Components in 2ZRX
Label Count Molecule
Proteins (4 molecules)
Isopentenyl-diphosphate Delta-isomerase
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

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