1GR0

myo-inositol 1-phosphate synthase from Mycobacterium tuberculosis in complex with NAD and zinc.

Summary for 1GR0

• Entry DOI: 10.2210/pdb1gr0/pdb
• Descriptor: INOSITOL-3-PHOSPHATE SYNTHASE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ZINC ION, ... (5 entities in total)
• Functional Keywords: isomerase, oxidoreductase, psi, protein structure initiative, tb structural genomics consortium, tb, tbsgc
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 1
• Total formula weight: 41005.32

Authors

Norman, R.A.,Murray-Rust, J.,McDonald, N.Q.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2001-12-10, release date: 2002-03-12, Last modification date: 2024-05-01)

Primary citation

Norman, R.A.,Mcalister, M.S.B.,Murray-Rust, J.,Movahedzadeh, F.,Stoker, N.G.,Mcdonald, N.Q.
Crystal Structure of Inositol 1-Phosphate Synthase from Mycobacterium Tuberculosis, a Key Enzyme in Phosphatidylinositol Synthesis
Structure, 10:393-, 2002

PubMed Abstract: Phosphatidylinositol (PI) is essential for Mycobacterium tuberculosis viability and the enzymes involved in the PI biosynthetic pathway are potential antimycobacterial agents for which little structural information is available. The rate-limiting step in the pathway is the production of (L)-myo-inositol 1-phosphate from (D)-glucose 6-phosphate, a complex reaction catalyzed by the enzyme inositol 1-phosphate synthase. We have determined the crystal structure of this enzyme from Mycobacterium tuberculosis (tbINO) at 1.95 A resolution, bound to the cofactor NAD+. The active site is located within a deep cleft at the junction between two domains. The unexpected presence of a zinc ion here suggests a mechanistic difference from the eukaryotic inositol synthases, which are stimulated by monovalent cations, that may be exploitable in developing selective inhibitors of tbINO.

PubMed: 12005437
DOI: 10.1016/S0969-2126(02)00718-9

Experimental method

X-RAY DIFFRACTION (1.95 Å)