4E1A

Phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis at 1.62A resolution

Summary for 4E1A

• Entry DOI: 10.2210/pdb4e1a/pdb
• Descriptor: Phosphopantetheine adenylyltransferase, GLYCEROL (3 entities in total)
• Functional Keywords: transferase
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cytoplasm (By similarity): P0A530
• Total number of polymer chains: 1
• Total formula weight: 17740.35

Authors

Timofeev, V.I.,Smirnova, E.A.,Chupova, L.A.,Esipov, R.S.,Kuranova, I.P. (deposition date: 2012-03-06, release date: 2012-11-21, Last modification date: 2024-02-28)

Primary citation

Timofeev, V.,Smirnova, E.,Chupova, L.,Esipov, R.,Kuranova, I.
X-ray study of the conformational changes in the molecule of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis during the catalyzed reaction.
Acta Crystallogr.,Sect.D, 68:1660-1670, 2012

PubMed Abstract: Structures of recombinant phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium tuberculosis (PPATMt) in the apo form and in complex with the substrate ATP were determined at 1.62 and 1.70 Å resolution, respectively, using crystals grown in microgravity by the counter-diffusion method. The ATP molecule of the PPATMt-ATP complex was located with full occupancy in the active-site cavity. Comparison of the solved structures with previously determined structures of PPATMt complexed with the reaction product dephosphocoenzyme A (dPCoA) and the feedback inhibitor coenzyme A (CoA) was performed using superposition on C(α) atoms. The peculiarities of the arrangement of the ligands in the active-site cavity of PPATMt are described. The conformational states of the PPAT molecule in the consequent steps of the catalyzed reaction in the apo enzyme and the enzyme-substrate and enzyme-product complexes are characterized. It is shown that the binding of ATP and dPCoA induces the rearrangement of a short part of the polypeptide chain restricting the active-site cavity in the subunits of the hexameric enzyme molecule. The changes in the quaternary structure caused by this rearrangement are accompanied by a variation of the size of the inner water-filled channel which crosses the PPAT molecule along the threefold axis of the hexamer. The molecular mechanism of the observed changes is described.

PubMed: 23151631
DOI: 10.1107/S0907444912040206

Experimental method

X-RAY DIFFRACTION (1.62 Å)