2ZRV

Crystal structure of Sulfolobus shibatae isopentenyl diphosphate isomerase in complex with reduced FMN.

Summary for 2ZRV

• Entry DOI: 10.2210/pdb2zrv/pdb
• Related: 2ZRU 2ZRW 2ZRX 2ZRY 2ZRZ
• Descriptor: Isopentenyl-diphosphate delta-isomerase, 1-DEOXY-1-(7,8-DIMETHYL-2,4-DIOXO-3,4-DIHYDRO-2H-BENZO[G]PTERIDIN-1-ID-10(5H)-YL)-5-O-PHOSPHONATO-D-RIBITOL (3 entities in total)
• Functional Keywords: type 2, idi, fmn, isopentenyl diphosphate isomerase, reduced form, flavoprotein, isomerase, isoprene biosynthesis, nadp
• Biological source: Sulfolobus shibatae
• Cellular location: Cytoplasm (By similarity): P61615
• Total number of polymer chains: 4
• Total formula weight: 163736.70

Authors

Unno, H.,Yamashita, S.,Ikeda, Y.,Sekiguchi, S.,Yoshida, N.,Yoshimura, T.,Kusunoki, M.,Nakayama, T.,Nishino, T.,Hemmi, H. (deposition date: 2008-09-01, release date: 2009-01-20, Last modification date: 2024-03-13)

Primary citation

Unno, H.,Yamashita, S.,Ikeda, Y.,Sekiguchi, S.Y.,Yoshida, N.,Yoshimura, T.,Kusunoki, M.,Nakayama, T.,Nishino, T.,Hemmi, H.
New role of flavin as a general acid-base catalyst with no redox function in type 2 isopentenyl-diphosphate isomerase.
J.Biol.Chem., 284:9160-9167, 2009

PubMed Abstract: 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.

PubMed: 19158086
DOI: 10.1074/jbc.M808438200

Experimental method

X-RAY DIFFRACTION (2.3 Å)