1U1I

Myo-inositol phosphate synthase mIPS from A. fulgidus

Summary for 1U1I

• Entry DOI: 10.2210/pdb1u1i/pdb
• Related: 1gr0 1jkf
• Descriptor: myo-inositol-1-phosphate synthase, PHOSPHATE ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: nad cofactor, metal ions, isomerase
• Biological source: Archaeoglobus fulgidus
• Total number of polymer chains: 4
• Total formula weight: 178180.40

Authors

Stieglitz, K.A.,Yang, H.,Roberts, M.F.,Stec, B. (deposition date: 2004-07-15, release date: 2004-08-10, Last modification date: 2023-08-23)

Primary citation

Stieglitz, K.A.,Yang, H.,Roberts, M.F.,Stec, B.
Reaching for Mechanistic Consensus Across Life Kingdoms: Structure and Insights into Catalysis of the myo-Inositol-1-phosphate Synthase (mIPS) from Archaeoglobus fulgidus
Biochemistry, 44:213-224, 2005

PubMed Abstract: myo-Inositol-1-phosphate synthase (mIPS) catalyzes the first step in the synthesis of l-myo-inositol-1-phosphate. We have solved and refined the structure of the mIPS from the hyperthermophilic sulfate reducer Archaeoglobus fulgidus at 1.9 A resolution. The enzyme crystallized from poly(ethylene glycol) in the P1 space group with one tetramer in the asymmetric unit and provided a view of the entire biologically active oligomer. Despite significant changes in sequence length and amino acid composition, the general architecture of the archaeal enzyme is similar to that of the eukaryotic mIPS from Saccharomyces cerevisiae and bacterial mIPS from Mycobacterium tuberculosis. The enhanced thermostability of the archaeal enzyme as compared to that from yeast is consistent with deletion of a number of surface loops that results in a significantly smaller protein. In the structure of the A. fulgidus mIPS, the active sites of all four subunits were fully ordered and contained NAD(+) and inorganic phosphate. The structure also contained a single metal ion (identified as K(+)) in two of the four subunits. The analysis of the electrostatic potential maps of the protein suggested the presence of a second metal-ion-binding site in close proximity to the first metal ion and NAD(+). The modeling of the substrate and known inhibitors suggests a critical role for the second metal ion in catalysis and provides insights into the common elements of the catalytic cycle in enzymes from different life kingdoms.

PubMed: 15628862
DOI: 10.1021/bi048267o

Experimental method

X-RAY DIFFRACTION (1.9 Å)