2a84
Crystal structure of A Pantothenate synthetase complexed with ATP
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OverviewOverview
Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a, potential target for antituberculosis drugs. PS catalyzes the, ATP-dependent condensation of pantoate and beta-alanine to form, pantothenate. Previously, we determined the crystal structure of PS from, M. tuberculosis and its complexes with AMPCPP, pantoate, and pantoyl, adenylate. Here, we describe the crystal structure of this enzyme, complexed with AMP and its last substrate, beta-alanine, and show that the, phosphate group of AMP serves as an anchor for the binding of, beta-alanine. This structure confirms that binding of beta-alanine in the, active site cavity can occur only after formation of the pantoyl adenylate, intermediate. A new crystal form was also obtained; it displays the, flexible wall of the active site cavity in a conformation incapable of, binding pantoate. Soaking of this crystal form with ATP and pantoate gives, a fully occupied complex of PS with ATP. Crystal structures of these, complexes with substrates, the reaction intermediate, and the reaction, product AMP provide a step-by-step view of the PS-catalyzed reaction. A, detailed reaction mechanism and its implications for inhibitor design are, discussed.
About this StructureAbout this Structure
2A84 is a Single protein structure of sequence from Mycobacterium tuberculosis with MG, ATP and GOL as ligands. Active as Pantoate--beta-alanine ligase, with EC number 6.3.2.1 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action., Wang S, Eisenberg D, Biochemistry. 2006 Feb 14;45(6):1554-61. PMID:16460002
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